Next Article in Journal
Modulation of the Tissue Expression Pattern of Zebrafish CRP-Like Molecules Suggests a Relevant Antiviral Role in Fish Skin
Previous Article in Journal
The Role of Serum 5-HIAA as a Predictor of Progression and an Alternative to 24-h Urine 5-HIAA in Well-Differentiated Neuroendocrine Neoplasms
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Biology
Volume 10
Issue 2
10.3390/biology10020077
biology-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise

by
Daniela D’Amico
1,2,†,
Roberto Fiore
3,†,
Daniela Caporossi
4,
Valentina Di Felice
1,
Francesco Cappello
1,5,*,
Ivan Dimauro
4,*,‡ and
Rosario Barone
1,*,‡
1
Human Anatomy Section, Department of Biomedicine, Neuroscience and Advanced Diagnostics (BiND), University of Palermo, 90127 Palermo, Italy
2
Department of Neuroscience, Cell Biology, and Anatomy, University of Texas Medical Branch (UTMB), Galveston, TX 77554, USA
3
Postgraduate School of Sports Medicine, University Hospital of Palermo, 90127 Palermo, Italy
4
Department of Movement, Human and Health Sciences, University of Rome Foro Italico, 00135 Rome, Italy
5
Euro-Mediterranean Institutes of Science and Technology (IEMEST), 90139 Palermo, Italy
*
Authors to whom correspondence should be addressed.
†
These authors contributed equally to this work.
‡
These authors contributed equally to this work.
Biology 2021, 10(2), 77; https://doi.org/10.3390/biology10020077
Submission received: 20 December 2020 / Revised: 15 January 2021 / Accepted: 19 January 2021 / Published: 21 January 2021
Review Reports Versions Notes

Abstract

:

Simple Summary

Skeletal muscle represents about 40% of the body mass in humans and it is a copious and plastic tissue, rich in proteins that are subject to continuous rearrangements. Physical exercise is considered a physiological stressor for different organs, in particular for skeletal muscle, and it is a factor able to stimulate the cellular remodeling processes related to the phenomenon of adaptation. All cells respond to various stress conditions by up-regulating the expression and/or activation of a group of proteins called heat shock proteins (HSPs). Although their expression is induced by several stimuli, they are commonly recognized as HSPs due to the first experiments showing their increased transcription after application of heat shock. These proteins are molecular chaperones mainly involved in assisting protein transport and folding, assembling multimolecular complexes, and triggering protein degradation by proteasome. Among the HSPs, a special attention needs to be devoted to Hsp60 and αB-crystallin, proteins constitutively expressed in the skeletal muscle, where they are known to be important in muscle physiopathology. Therefore, here we provide a critical update on their role in skeletal muscle fibers after physical exercise, highlighting the control of their expression, their biological function, and their specific distribution within skeletal muscle fiber-types.

Abstract

Skeletal muscle is a plastic and complex tissue, rich in proteins that are subject to continuous rearrangements. Skeletal muscle homeostasis can be affected by different types of stresses, including physical activity, a physiological stressor able to stimulate a robust increase in different heat shock proteins (HSPs). The modulation of these proteins appears to be fundamental in facilitating the cellular remodeling processes related to the phenomenon of training adaptations such as hypertrophy, increased oxidative capacity, and mitochondrial activity. Among the HSPs, a special attention needs to be devoted to Hsp60 and αB-crystallin (CRYAB), proteins constitutively expressed in the skeletal muscle, where their specific features could be highly relevant in understanding the impact of different volumes of training regimes on myofiber types and in explaining the complex picture of exercise-induced mechanical strain and damaging conditions on fiber population. This knowledge could lead to a better personalization of training protocols with an optimal non-harmful workload in populations of individuals with different needs and healthy status. Here, we introduce for the first time to the reader these peculiar HSPs from the perspective of exercise response, highlighting the control of their expression, biological function, and specific distribution within skeletal muscle fiber-types.

1. Introduction

All organisms and cells respond to various stress conditions by up-regulating the expression and/or activation of a group of proteins called heat shock proteins (HSPs). Although their expression is induced by several stimuli [1], they are commonly recognized as HSPs due to the first experiments showing their increased transcription after application of heat shock [2,3,4]. These proteins are molecular chaperones mainly involved in assisting protein transport and folding, assembling multimolecular complexes, and triggering protein degradation by proteasome. In addition, they play a crucial role in gene expression regulation, DNA replication, signal transduction, cell differentiation, apoptosis, cellular senescence or immortalization, and intercellular communications [5,6,7,8]. Heat shock proteins are classified according to their molecular weight in super heavy, 100, 90, 70, 60, 40, and small HSPs [9]. Although they are the most highly conserved, ubiquitous, and abundant proteins in all organisms, their cellular stress response can depend on the class and stimulus.
Physical exercise is considered a physiological stress factor able to stimulate a robust increase in different HSPs in several tissues, which appears to be fundamental in facilitating the cellular remodeling processes related to the phenomenon of adaptation [10].
Skeletal muscle, which represents about 40% of the body mass in humans, is a copious and plastic tissue [11,12,13,14], which largely responds to physical exercise and needs the HSP chaperoning system to control intracellular components and communications [15,16]. Indeed, it is widely accepted that exercise modulates the activity and the expression of HSPs in skeletal muscles depending on the characteristics of exercise program (i.e., type, intensity duration, and frequency) [17,18,19,20,21]. The exercise-induced changes in HSPs seem to have multiple cytoprotective effects on mitochondria, sarcoplasmic reticulum and cytoskeleton components [22,23,24], inhibitory effects on apoptosis [25], as well as a role in the maintenance of enzymatic activity, insulin sensitivity, and glucose transport [26,27].
Among the HSPs, special attention needs to be devoted to Hsp60 (HSPD1) and αB-crystallin (CRYAB, HSPB1), proteins constitutively expressed in the skeletal muscle, where they are known to be important in muscle physiopathology [28,29,30,31,32]. Therefore, given the emerging role in general health and the disease conditions of Hsp60 and CRYAB, here we provide a critical update on their role in skeletal muscle fibers after physical exercise, highlighting the control of their expression, their biological function, and their specific distribution within skeletal muscle fiber-types.

2. Fiber-Types of Skeletal Muscle and Its Adaptation to Physical Exercise

Skeletal muscle is a heterogeneous tissue containing fibers with different morphological, metabolic, and functional properties. Muscle fibers are typically identified by the expression of a multigene family of Myosin Heavy Chains (MHCs). Their sequence variability has been associated with their specific structure and function, but the codified actin-based motor proteins are conserved [33,34]. In the skeletal muscle they are classified as MHC-I, MHC-IIa, MHC-IIx, and MHC-IIb [33,34,35]. The MHC-I, IIa, and IIx fiber-types are expressed to variable degrees in both small animals (mice, rats, and rabbits) and human skeletal muscle. Instead, MHC-IIb fibers are solely expressed in small animals’ skeletal muscle [21]. In mammals, ‘‘hybrid’’ fibers (i.e., type I/IIa, IIa/x, IIx/b) can occur when different MHC transcripts coexist in a single fiber [12,36,37].
Although the structural and functional muscle requests define privileged associations between MHC isoforms, other common fiber-type classifications are used. One of them is related to the contractile response (or speed of contraction) distinguishing between slow or fast muscle fibers. In addition, cellular metabolism has been used as another parameter to distinguish the different types of myofibers with glycolytic metabolism and fibers with a massive mitochondrial presence and prevalent aerobic metabolism. Notably, MHC isoform expression correlates with fiber-type morphology, metabolism, and function [38,39]. In general terms, MHC-I-expressing fibers are small, rich in oxidative enzymes, slow in contraction, and have a greater resistance to fatigue, while MHC-IIb-expressing fibers are large, rich in glycolytic enzymes, and fast in contraction due to the developed sarcoplasmic reticulum that allows the rapid release of calcium ions, and a predominantly anaerobic metabolism [40,41]. Specifically, fiber contraction correlates with myosin ATPase activity with relative velocities of I < IIa < IIx < IIb [42,43]. Furthermore, skeletal muscle can be classified as postural or non-postural according to its function and the percentage of each fiber-type [44]. Although the four main types of skeletal muscle fibers are present in different percentages among the mammal species and within the same species therein, they are represented differently in the various structures of the musculoskeletal system (Table 1) [45,46,47,48]. Moreover, basal mitochondrial content has been shown to vary between species and is fiber-type-specific in mouse, rat, and human skeletal muscles [49].
One of the most surprising characteristics of the myofibers of the skeletal muscle is the high degree of plasticity as an adaptive response to physiological and non-physiological requests [50]. Plasticity is the ability of a tissue to modify its composition by adapting it to changing functional needs. Repeated, prolonged, or simple changes in functional requests can both quantitatively and qualitatively modify muscle tissue. These changes can affect the myofibrillary system, the sarcoplasmic reticulum, the proteins involved in regulating the concentration of intracellular calcium as well as the enzymatic systems involved in energy metabolism. The mechanism of adaptation of the functional requests is based primarily on the transformation of the MHC content, with a shift of the MHC fibers that affects the overall speed of contraction of the muscle. However, it is also possible that an increase in the speed of the same cellular type occurs in the absence of variations of the expressed MHC isoforms [51,52]. The increased contractile activity following physical exercise activates several signal pathways that lead to significant phenotypic changes such as MHC fiber transitions, enhanced mitochondrial biogenesis, and angiogenesis. Changes in the expression pattern of MHC isoforms and in the cross-sectional area (CSA) of the skeletal muscle cells, in response to different training protocols, are related to the changes in strength and power that the muscle undergoes [53]. For these reasons, physical exercise induces muscle hypertrophy that is followed by the upregulation of contractile elements’ synthesis. Literature data have shown the hypertrophic response for all three major types of fibers (MCH-I, IIa, and IIx) following resistance training, both in young subjects and in elderly subjects [54]. However, exercise-induced hypertrophy seems to affect fast muscle fibers more than type I fibers [55]. Exercise can therefore induce changes in the expression of MHCs, thus causing a switch from type IIb to IIx and IIa and, in rare cases, also to type I. In most cases, physiological adaptations to increased activity induce a switch to a more oxidative fast phenotype [35]. Allen et al. showed a significant increase in the percentage of fibers expressing MHC-IIa and a concomitant decrease in the percentage of fibers expressing MHC-IIb in mouse fast muscles after some weeks of wheel exercise [56]. The switch in the range IIb–IIx–IIa in mouse and rat muscle or in the range IIx–IIa in human muscle likely reflects the total amount of activity [57].
Human studies have shown that strength training induces an increase in type IIa and hybrid IIa/x fibers at the expense of fast IIx fibers. At the same time, there is an increase in the CSA in all types of myofibers, indicating a hypertrophic effect [58]. In fact, Kesidis et al. showed that type IIa muscle fibers in human skeletal muscle seem to have an enzymatic profile and a rate of contraction that makes these fibers more suitable for strength performance than fibers containing the MHC I isoform [59]. On the other hand, endurance training seems to induce fast-to-slow fiber transitions (from IIx to IIa, and in rare cases type I), while the CSA values remain unchanged. The physiological advantage is the greater transduction efficiency of the mechanical energy associated with the IIa fibers compared to the IIx fibers. However, the increased proportion of type I fibers could derive from different training protocols, causing a significant turnover and regeneration of fibers, and also including a regeneration of the peripheral nerve [60]. The absence of cellular damage can be explained by the lack of the expression of embryonic myosin isoforms and supports the results of the studies in which no variations in fiber-type I following training protocols were detected [61].

3. Stress Proteins: Heat Shock Protein 60

The HSPD1 gene comprises ~17 kb with 12 exons and it is localized at chromosome locus 2q33.1. This gene encodes a protein of 573aa corresponding to a molecular weight of 61.05 kDa known as HSP60 or Hsp60, also commonly referred to as Cpn60 [62]. Hsp60 belongs to group I of chaperonins [63]. Its ATP-dependent chaperon mechanism was thoroughly investigated for the prokaryotic homolog GroEL. Three structural domains were identified for GroEL: apical, intermediate, and equatorial. To carry out its chaperoning function, GroEL needs to generate a tetradecamer complex with its co-chaperon GroES (the homolog of Hsp10) [64]. Thus, the chaperon complex is made up of GroEL, structured in two rings with seven identical subunits, and GroES, which binds to the apical domains of GroEL to close the cage [65]. The chaperon mechanism is a multistep process that involves the unfolded protein binding to GroEL apical domains. Concomitantly, ATP binds to GroEL’s equatorial domain and its hydrolysis allows the conformational change (from trans to cis) of the GroEL apical and intermediate domains for the substrate encapsulation in the central cavity of the chaperon [66]. Consecutively, the dissociation of the cis-complex and the release of the folded protein, ADP, and GroES occurs [67]. Although the chaperon mechanism of the mammalian mitochondrial Hsp60-Hsp10 complex is similar, the solid-state structure appears as a symmetrical football-shaped complex by X-ray [68]. In humans, the mitochondrial Hsp60 exists as a homo-oligomer of seven subunits in equilibrium with very minor populations of monomers and double-ring tetradecamers [69,70]. In addition, it was demonstrated that Hsp60 single ring could perform chaperonin-mediated folding activity in vivo [71].
Hsp60 is constitutively expressed under philological conditions, so much so that its knockout is incompatible with life [72,73,74]. At the same time, Hsp60 expression is related to numerous etio-pathological conditions [75]. Hsp60 is mainly localized in the mitochondria. The mitochondrial import signal (MIS) at the N-terminus drives Hsp60 from the cytoplasm to the mitochondria [76]. Nevertheless, one third of Hsp60 is localized to the extra-mitochondrial sites, such as cytosol, plasma-cell membrane, inside exosomes, extracellular space, and circulation [77,78]. Inside the mitochondria, Hsp60 guarantees the correct folding of other mitochondrial proteins [7,79] as well as its “unfoldase” activity to stabilize misfolded and aggregated proteins, making provision for the mitochondrial biogenesis and protein homeostasis [80,81]. In addition, the mitochondrial Hsp60 directs the replication and transmission of mitochondrial DNA (mtDNA) [82,83]. Otherwise, the extramitochondrial Hsp60 is involved in intracellular protein trafficking [84] and peptide-hormone signaling [85]. Interestingly, the mitochondrial and the cytosolic Hsp60 have a contradictory role in pro-apoptotic and pro-survival mechanisms [86]. Whether Hsp60 is associated with carcinogenesis, specifically with tumor cell survival and proliferation, for certain tumors is used as a good diagnostic marker [87,88,89,90]. Therefore, Hsp60 exerts divergent roles in several physiological and pathological processes, and an understanding of its structural and functional biology aspires to draw novel pathways and to develop therapeutic strategies.

4. Stress Proteins: αB-Crystallin

HSPB1, or the CRYAB gene, encodes a 175-amino acid protein with a molecular mass of ~20 kDa [91]. CRYAB is a ubiquitous sHSP with highly conserved stretch that adopts a β-sandwich, immunoglobulin-like fold called the “α-crystallin domain (ACD),” which is a characteristic hallmark of the sHSPs family [92]. The ACD region is flanked by a less conserved and flexible N-terminal domain (NTD) and a C-Terminal extension (CTE), which are variable in length and sequence except for few conserved stretches [92,93].
Based on all findings related to CRYAB missense, truncating, and frame-shift mutations, specific functional roles of these domains have been hypothesized. Indeed, mutations within ACD domain (i.e., D109H/D109A, R120G) seem to interfere with the CRYAB oligomerization processes [94,95,96], while those within the CTE domain (i.e., 464delCT, R151X, G154S, L155fs_163X, R157H) seem to compromise CRYAB chaperone function [25,97,98,99,100,101]. Finally, mutations within the NTD domain seem to prevent the building of higher order oligomeric structures [102]. Thus, oligomeric assembly and chaperone activity of CRYAB is inter-dependent on its NTD, ACD and CTE domains.
As all sHSPs do, CRYAB shares in the property to form globular oligomer structures that in mammalian cells are characterized by molecular masses ranging from 50 to about 800 kDa. This ability, together with the well-known hetero-oligomerization property, is crucial factor in regulating the activity of this protein [103]. This hetero oligomer is probably unable to play an efficient protective role in stress conditions. However, the dissociation of the complex after-exposure to heat shock or oxidative stress suggests that it could bear new protein target recognition abilities and/or modulate those of the parental molecules [104].
Another intriguing property of sHSPs concerns its ability to be phosphorylated and therefore susceptible of control by several transduction pathways. Depending on the type and/or duration of various stimuli, the fraction of phosphorylated CRYAB ranges between 10% and 27% [105,106]. Different studies demonstrate that the phosphorylation of CRYAB shows a dual role that leads to either beneficial or deleterious outcomes depending on the extent and duration of stress and subsequent degree of phosphorylation; a phosphorylation at initial stage of stress is usually reversible and seems to provide a beneficial outcome, while prolonged stress can induce an irreversible phosphorylation which may lead to a deleterious outcome [107]. The CRYAB has three phosphorylation sites (S19, S45, and S59) at the NTD, which play a critical role in the protein functions. While the phosphorylation on S59 is mediated by p38 mitogen-activated protein kinase (p38 MAPK) and phosphorylation on S45 by the extracellular signal-regulated kinase 1/2 (ERK1/2) [106,108], the kinase responsible for phosphorylation on S19 is still unknown. Nevertheless, both unphosphorylated and phosphorylated forms of CRYAB are reported to be equally effective in preventing in vitro assembly of glial fibrillary acidic protein and vimentin in an ATP-independent manner [109]. In fact, during physiological or pathological stress both CRYAB content and phosphorylation can be modulated [29,110,111,112,113].
All aforementioned serine residues can be phosphorylated after various stimuli [106], but only a few studies have reported their contemporary involvement in muscle tissues [32,113,114,115,116]. To date, most of the available data are related to CRYAB expression and/or activation at Ser59 [29,110,117,118,119,120,121,122]. Moreover, the relationship between the phosphorylation of CRYAB and its chaperone activity is contradictory. Though in general the phosphorylation has an augmentative effect, it is possible that modulation of the activity upon phosphorylation might depend on the target protein and its interactions [123]. Further details about the phosphorylation of CRYAB in various physiological or pathological conditions can be found elsewhere [107,124].
In addition to being overexpressed in stress conditions, CRYAB shares the ability of having a tissue/cell-specific expression in the absence of stress, which can be detected in healthy adults as well as during organism development [125]. In mammalian cells, CRYAB is constitutively expressed in tissue with high rates of oxidative metabolism, including the cardiac and skeletal muscle [126]. The significance of the constitutive expression of this sHSP is probably linked to the protection of the cells against chronic stress or to a specific function in a particular tissue.

5. Hsp60 in Skeletal Muscle Fibers

The chaperoning systems that participate in controlling cellular homeostasis have been detected in skeletal muscle. Small Hsp, Hsp60, Hsp70, and Hsp90 play a significant role in muscle adaptation [17,127]. Nevertheless, Hsp60 was not deeply investigated after physical exercise, which, as we have already discussed, influences muscle homeostasis [77]. Hsp60 and exercise correlation appears to be rational, but literature data are restricted and sometimes controversial (Table 2). Morton et al. [128] demonstrated that aerobically trained men had significantly higher resting levels of Hsp60 in the vastus lateralis muscle (high percentage of fibers I and IIa) compared to untrained subjects, suggesting Hsp60 as a molecular marker of physiological adaptation to aerobic exercise. However, it has been demonstrated that in the human vastus lateralis muscle the highest mitochondrial content is showed by type I fibers followed by type IIa > IIx (Table 1) [49]. At the same time, an acute single bout of endurance training that is considered an aerobic exercise did not increase the basal Hsp60 protein levels in the same muscle [128]. Thus, chronic training has the capacity to increase Hsp60 expression, whereas a single bout of exercise does not. Hsp60 expression is stimulated by endurance, resistance, and mixed training, but its fiber specificity is still debated. Hsp60 expression in the vastus lateralis of healthy active people with different training backgrounds was considered not to be fiber-type specific [129]. In agreement, Ogata et al. [130] and Soares Moura et al. [131] did not show significant differences in Hsp60 levels in the plantaris and gastrocnemius, both rich fiber IIx muscles, of male rats after endurance training. On the other hand, several groups, including ours, demonstrated fiber-type specificity after training in specific muscles. Mattson et al. [132] showed that female rats trained with an endurance protocol for 8 weeks displayed significantly higher levels of Hsp60 in the muscle plantaris, which is rich in fiber-type IIb [46]. No difference of Hsp60 levels was detected in the rich fiber I muscle soleus in endurance-trained rats compared to the untrained group [47,132]. Hsp60 fiber-type I specificity was reported by Samelman [133], who showed increased basal levels of Hsp60 in the soleus and not in the lateral gastrocnemius of endurance trained rats. In agreement, our group noted Hsp60 fiber-specific expression in healthy male BALB/c mice trained for 45 days on the treadmill. Specifically, higher levels of Hsp60 were observed in type I and IIa muscle fibers, while type IIx and IIb fibers showed a constitutive expression of this chaperonin [134]. Therefore, increased levels of Hsp60 were reported after six weeks of endurance training, mainly in red gastrocnemius and soleus muscles, which are particularly rich in type I and IIa fibers [134]. We also correlated this physiological adaptation to an increased expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), which triggers the mitochondrial biogenesis and thereby avoiding the cytotoxic effects [134,135,136]. Finally, increased levels of Hsp60 were observed in the soleus muscle of male mice and the Extensor Digitorum Longus (EDL) muscle of female mice after an acute single bout of endurance training [48].

6. αB-Crystallin in Skeletal Muscle Fibers

CRYAB is a protein highly expressed in slow and fast fibers of adult skeletal muscle where it is associated with actin microfilaments at level of Z-bands [98]. Different lines of evidence suggest that this sHSP protects the skeletal muscle from heat, oxidative, and mechanical stresses produced during physical activity [32,110,137,138,139].
At the molecular level, it has been demonstrated that the alteration of any of the three major components (i.e., microfilaments, microtubules, and intermediate filaments) results in a specific activation of p38MAPK and MAPKAP kinases 2 and 3 and the phosphorylation of CRYAB [115]. Our group also demonstrated that a reversible redox unbalance, which represents one of the main stimuli under different circumstances, including physical activity, induces CRYAB expression through a JNK-mediated transcriptional mechanism in myogenic cells [110]. On the one hand, the increased level of CRYAB and its phosphorylation determine its translocation to the myofilaments where it binds titin, desmin, vimentin, nebulette, filamin A, and the inactive precursor of caspase 3, leading to the stabilization of the myofilament and to the inhibition of apoptosis [29,32]; on the other side, it enhances NFκB activity, which translocates into the nucleus, inducing the expression of genes involved in various biological events such as growth, differentiation, and cell death [29,140,141].
Moreover, CRYAB appears to have a role in regulation of apoptosis during heat shock, oxidative stress, and ischemia. This protein is able to prevent apoptosis by several mechanisms such as the inhibition of RAS-initiated RAF/MEK/ERK signaling pathway [142], or downstream, blocking the BAX and Bcl-2 translocation from cytoplasm to mitochondria [143], as well as interacting with p53 to retain it in the cytoplasm [144] or inhibiting autocatalytic maturation of caspase-3 [145].
A recent finding has established that CRYAB is necessary for a correct skeletal muscle homeostasis via modulation of Argonaute 2 (Ago2) activity [120], a protein with endonuclease activity. It belongs to the central core of RNA-induced silencing complex (RISC), capable to repress the translation of mRNA into protein via a variety of mechanisms such as removal of the of the 5-7-methylguanylate cap (m7G), deadenylation of the 3′-poly(A) tail, and miRNA site-directed endonuclease cleavage of the mRNA [146,147]. This result indicates that CRYAB functions as a positive allosteric regulator of Ago2/RISC. In fact, the absence of CRYAB results in the unbalance of hypertrophy-atrophy axis toward atrophy with an excessive miRNA loading into Ago2/RISC [120].
The study of the distribution of CRYAB in skeletal muscle dates back to the early 1990s [148,149]. Subsequently, other authors investigated the distribution of this sHSP in skeletal muscle even in pathological conditions [150,151]. In mammalian studies, all studies agree that CRYAB is predominantly expressed in oxidative muscle fibers (type I and IIa) [148,149,150,151].
Despite the paucity of the number of studies in the field of physical activity and distribution of CRYAB in muscle fibers, exercise-based studies analyzing the modulation of this sHSP in humans and rodents reported a modulation of CRYAB dependent from the characteristics of exercise. It was observed that this sHSP was up-regulated depending on the damaging nature of exercise. Indeed, in non-damaging conditions, the CRYAB protein level was unchanged independently from the skeletal muscle examined [21,32,129,152], whereas following an exercise associated with damage to strain-bearing cell structures, CRYAB was significantly up-regulated [129,153,154,155] (Table 3). In contrast, the phosphorylation form of CRYAB was found increased in muscles with the highest percentage of type I fibers, independently from the type (endurance or resistance) and nature (damaging or not) of exercise [32,129,155,156] (Table 3).
The analysis of fiber-type-specific expression/activation of CRYAB has revealed that its redistribution within skeletal muscles is influenced by different physical activity regimes [32,129,156]. In particular, a higher staining intensity of CRYAB was found in type I compared to type II fibers, which was in line with previous results obtained in rodents, where a stronger CRYAB expression was found in slow oxidative muscle fibers [157,158]. However, Folkesson and colleagues show a similar staining intensity of CRYAB between type II and type I fibers in well-trained endurance athletes [129]. A similar fiber type-specific increase in CRYAB has been shown in rabbit tibialis anterior muscles following 21 days of continuous low-frequency motor nerve stimulation, which keeps the fiber-specific pattern of CRYAB from being expressed only in type I fibers and in a subpopulation of type II fibers, to be expressed in nearly all fibers [157]. Recently, our group has shown that following an acute non-damaging endurance exercise, the phosphorylation level of this sHSP was significantly increased only in skeletal muscle with a higher amount of type I and IIA/X myofibers. In particular, the phosphorylation level of CRYAB was apparently related to the percentage of type I and IIA/X myofibers contained in slow twitch and mixed muscles (i.e., the soleus and red gastrocnemius). In support of the aforementioned data, Jacko and colleagues demonstrated that a multiple set of resistance exercises increases the phosphorylation level of CRYAB in type I myofibers of the vastus lateralis independently from the load volume, while in the type II fibers the phosphorylation was observed only after high force demanding loadings [156].
These results could reflect the role of CRYAB in counteracting homeostatic perturbations, including mechanical, thermal, and oxidative stress induced by physical exercise, as well as to reinforce the idea that the phosphorylation of CRYAB in these tissues possibly reflects the level of stress experienced by the muscle.

7. Summary and Conclusions

There is substantial evidence that regular physical activity promotes health and healthy aging [118,138,159,160,161]. In particular, we know from our work and that of other laboratories that trained subjects show an adaptive response at both systemic and cellular levels through the modulation of antioxidants and stress-induced proteins, such as HSPs, as well as an improvement of other parameters strictly correlated to the healthy status [162,163,164,165,166,167,168]. Moreover, it is known that exercise induced-adaptation in mammalian skeletal muscle, and in other tissues, is related to training mode and can be fiber-type specific.
In this review, we highlighted for the first time the regulation and function of Hsp60 and CRYAB, as well as their different expression/activation in skeletal muscle fibers in response to exercise. The determination of a fiber-type-specific expression of Hsp60 and CRYAB could be important to comprehend the impact of different volumes of training regimes on myofiber types and explains the complex picture of exercise-induced mechanical strain and damaging conditions on fiber population.
In summary, Hsp60 was found to be exclusively up-regulated in skeletal muscles rich in slow and fast oxidative fibers that were aerobically trained (endurance exercise), with a distribution not fiber-specific following other training regimes (e.g., resistance training). Similarly, CRYAB was mainly present in type I fibers, with an increase in its concentration in type II fibers depending on the individual’s fitness level. The phosphorylated form of this protein was more present in skeletal muscle with a higher amount of type I and IIA/X myofibers following endurance exercise, while its fiber-specificity appears to be dependent on the workload during resistance exercises.
This parallel behavior between Hsp60 and CRYAB within fiber-type distribution could be due to the involvement of CRYAB in the response to oxidative stress stimuli and the role of Hsp60 during the mitochondrial metabolism. In fact, the direct correlation between CRYAB and oxidative enzymes was already evident in the first studies on its cellular distribution [169].
Although further studies are recommended to clarify the role of these HSPs in muscle physiology, we strongly believe that this knowledge could lead to a better personalization of training protocols with an optimal non-harmful workload in people with different needs and healthy status. In the long term, the new knowledge will be expanded so to accumulate specific insight towards the effectiveness of muscle contraction patterns and the adaptive state of frequently loaded skeletal muscle, to be utilized in prevention, rehabilitation, and elite sports.

Author Contributions

D.D., R.F., I.D. and R.B. wrote the manuscript; R.B., I.D., V.D.F., D.C. and F.C. revised the manuscript. All authors have read and agreed to the published version of the manuscript.

Funding

This study was funded by “Ministero dell’Istruzione, dell’Università e della Ricerca” (PRIN2012-prot. 2012N8YJC3).

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Pockley, A.G.; Henderson, B. Extracellular cell stress (heat shock) proteins-immune responses and disease: An overview. Philos. Trans. R. Soc. Lond. Ser. B Biol. Sci. 2018, 373, 1738. [Google Scholar] [CrossRef] [Green Version]
  2. Ritossa, F. A new puffing pattern induced by temperature shock and DNP in Drosophila. Experientia 1962, 18, 571–573. [Google Scholar] [CrossRef]
  3. Tissieres, A.; Mitchell, H.K.; Tracy, U.M. Protein synthesis in salivary glands of Drosophila melanogaster: Relation to chromosome puffs. J. Mol. Biol. 1974, 84, 389–398. [Google Scholar] [CrossRef]
  4. Mirault, M.E.; Goldschmidt-Clermont, M.; Moran, L.; Arrigo, A.P.; Tissieres, A. The effect of heat shock on gene expression in Drosophila melanogaster. Cold Spring Harb. Symp. Quant. Biol. 1978, 42, 819–827. [Google Scholar] [CrossRef]
  5. Czarnecka, A.M.; Campanella, C.; Zummo, G.; Cappello, F. Mitochondrial chaperones in cancer: From molecular biology to clinical diagnostics. Cancer Biol. Ther. 2006, 5, 714–720. [Google Scholar] [CrossRef] [Green Version]
  6. Georgopoulos, C.; Welch, W.J. Role of the major heat shock proteins as molecular chaperones. Annu. Rev. Cell Biol. 1993, 9, 601–634. [Google Scholar] [CrossRef]
  7. Voos, W. Chaperone-protease networks in mitochondrial protein homeostasis. Biochim. Biophys. Acta 2013, 1833, 388–399. [Google Scholar] [CrossRef] [Green Version]
  8. Henderson, B.; Calderwood, S.K.; Coates, A.R.; Cohen, I.; van Eden, W.; Lehner, T.; Pockley, A.G. Caught with their PAMPs down? The extracellular signalling actions of molecular chaperones are not due to microbial contaminants. Cell Stress Chaperones 2010, 15, 123–141. [Google Scholar] [CrossRef] [Green Version]
  9. Macario, A.J. Heat-shock proteins and molecular chaperones: Implications for pathogenesis, diagnostics, and therapeutics. Int. J. Clin. Lab. Res. 1995, 25, 59–70. [Google Scholar] [CrossRef]
  10. Kruger, K.; Reichel, T.; Zeilinger, C. Role of heat shock proteins 70/90 in exercise physiology and exercise immunology and their diagnostic potential in sports. J. Appl. Physiol. 2019, 126, 916–927. [Google Scholar] [CrossRef]
  11. Pette, D.; Staron, R.S. Cellular and molecular diversities of mammalian skeletal muscle fibers. Rev. Physiol. Biochem. Pharmacol. 1990, 116, 1–76. [Google Scholar] [PubMed]
  12. Schiaffino, S.; Reggiani, C. Myosin isoforms in mammalian skeletal muscle. J. Appl. Physiol. 1994, 77, 493–501. [Google Scholar] [CrossRef] [PubMed]
  13. Johnston, J.L.; Williams, C.N.; Weldon, K.L. Nutrient intake and meal patterns of Micmac indian and Caucasian women in Shubenacadie, NS. Can. Med. Assoc. J. 1977, 116, 1356–1359. [Google Scholar] [PubMed]
  14. Moss, R.L.; Diffee, G.M.; Greaser, M.L. Contractile properties of skeletal muscle fibers in relation to myofibrillar protein isoforms. Rev. Physiol. Biochem. Pharmacol. 1995, 126, 1–63. [Google Scholar]
  15. Hoppeler, H. Exercise-induced ultrastructural changes in skeletal muscle. Int. J. Sports Med. 1986, 7, 187–204. [Google Scholar] [CrossRef]
  16. Noble, E.G.; Milne, K.J.; Melling, C.W. Heat shock proteins and exercise: A primer. Appl. Physiol. Nutr. Metab. 2008, 33, 1050–1065. [Google Scholar] [CrossRef]
  17. Morton, J.P.; Kayani, A.C.; McArdle, A.; Drust, B. The exercise-induced stress response of skeletal muscle, with specific emphasis on humans. Sports Med. 2009, 39, 643–662. [Google Scholar] [CrossRef]
  18. Milne, K.J.; Noble, E.G. Exercise-induced elevation of HSP70 is intensity dependent. J. Appl. Physiol. (1985) 2002, 93, 561–568. [Google Scholar] [CrossRef] [Green Version]
  19. Puntschart, A.; Vogt, M.; Widmer, H.R.; Hoppeler, H.; Billeter, R. Hsp70 expression in human skeletal muscle after exercise. Acta Physiol. Scand. 1996, 157, 411–417. [Google Scholar] [CrossRef]
  20. Walsh, R.C.; Koukoulas, I.; Garnham, A.; Moseley, P.L.; Hargreaves, M.; Febbraio, M.A. Exercise increases serum Hsp72 in humans. Cell Stress Chaperones 2001, 6, 386–393. [Google Scholar] [CrossRef] [Green Version]
  21. Morton, J.P.; MacLaren, D.P.; Cable, N.T.; Bongers, T.; Griffiths, R.D.; Campbell, I.T.; Evans, L.; Kayani, A.; McArdle, A.; Drust, B. Time course and differential responses of the major heat shock protein families in human skeletal muscle following acute nondamaging treadmill exercise. J. Appl. Physiol. (1985) 2006, 101, 176–182. [Google Scholar] [CrossRef] [Green Version]
  22. Bornman, L.; Steinmann, C.M.; Gericke, G.S.; Polla, B.S. In vivo heat shock protects rat myocardial mitochondria. Biochem. Biophys Res. Commun. 1998, 29, 836–840. [Google Scholar] [CrossRef]
  23. Sammut, I.A.; Harrison, J.C. Cardiac mitochondrial complex activity is enhanced by heat shock proteins. Clin. Exp. Pharm. Physiol. 2003, 30, 110–115. [Google Scholar] [CrossRef]
  24. Tupling, A.R.; Gramolini, A.O.; Duhamel, T.A.; Kondo, H.; Asahi, M.; Tsuchiya, S.C.; Borrelli, M.J.; Lepock, J.R.; Otsu, K.; Hori, M.; et al. HSP70 binds to the fast-twitch skeletal muscle sarco(endo)plasmic reticulum Ca2+ -ATPase (SERCA1a) and prevents thermal inactivation. J. Biol. Chem. 2004, 10, 52382–52389. [Google Scholar] [CrossRef] [Green Version]
  25. Gabai, V.L.; Sherman, M.Y. Invited review: Interplay between molecular chaperones and signaling pathways in survival of heat shock. J. Appl. Physiol. (1985) 2002, 92, 1743–1748. [Google Scholar] [CrossRef] [Green Version]
  26. Melkani, G.C.; Cammarato, A.; Bernstein, S.I. alphaB-crystallin maintains skeletal muscle myosin enzymatic activity and prevents its aggregation under heat-shock stress. J. Mol. Biol. 2006, 5, 635–645. [Google Scholar] [CrossRef]
  27. Chung, J.; Nguyen, A.K.; Henstridge, D.C.; Holmes, A.G.; Chan, M.H.; Mesa, J.L.; Lancaster, G.I.; Southgate, R.J.; Bruce, C.R.; Duffy, S.J.; et al. HSP72 protects against obesity-induced insulin resistance. Proc. Natl. Acad. Sci. USA 2008, 5, 1739–1744. [Google Scholar] [CrossRef] [Green Version]
  28. Marino Gammazza, A.; Macaluso, F.; Di Felice, V.; Cappello, F.; Barone, R. Hsp60 in Skeletal Muscle Fiber Biogenesis and Homeostasis: From Physical Exercise to Skeletal Muscle Pathology. Cells 2018, 7, 224. [Google Scholar] [CrossRef] [Green Version]
  29. Adhikari, A.S.; Singh, B.N.; Rao, K.S.; Rao, C.M. αB-crystallin, a small heat shock protein, modulates NF-κB activity in a phosphorylation-dependent manner and protects muscle myoblasts from TNF-α induced cytotoxicity. Biochim. Biophys Acta 2011, 1813, 1532–1542. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  30. Dimauro, I.; Grasso, L.; Fittipaldi, S.; Fantini, C.; Mercatelli, N.; Racca, S.; Geuna, S.; Di Gianfrancesco, A.; Caporossi, D.; Pigozzi, F.; et al. Platelet-rich plasma and skeletal muscle healing: A molecular analysis of the early phases of the regeneration process in an experimental animal model. PLoS ONE 2014, 23, e102993. [Google Scholar] [CrossRef] [Green Version]
  31. Dimauro, I.; Antonioni, A.; Mercatelli, N.; Caporossi, D. The role of αB-crystallin in skeletal and cardiac muscle tissues. Cell Stress Chaperones 2018, 23, 491–505. [Google Scholar] [CrossRef] [PubMed]
  32. Dimauro, I.; Antonioni, A.; Mercatelli, N.; Grazioli, E.; Fantini, C.; Barone, R.; Macaluso, F.; Di Felice, V.; Caporossi, D. The early response of αB-crystallin to a single bout of aerobic exercise in mouse skeletal muscles depends upon fiber oxidative features. Redox Biol. 2019, 24, 101183. [Google Scholar] [CrossRef] [PubMed]
  33. Weiss, A.; McDonough, D.; Wertman, B.; Acakpo-Satchivi, L.; Montgomery, K.; Kucherlapati, R.; Leinwand, L.; Krauter, K. Organization of human and mouse skeletal myosin heavy chain gene clusters is highly conserved. Proc. Natl. Acad. Sci. USA 1999, 96, 2958–2963. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  34. Weiss, A.; Schiaffino, S.; Leinwand, L.A. Comparative sequence analysis of the complete human sarcomeric myosin heavy chain family: Implications for functional diversity. J. Mol. Biol. 1999, 290, 61–75. [Google Scholar] [CrossRef] [PubMed]
  35. Schiaffino, S.; Reggiani, C. Fiber types in mammalian skeletal muscles. Physiol. Rev. 2011, 91, 1447–1531. [Google Scholar] [CrossRef] [Green Version]
  36. Staron, R.S.; Pette, D. The continuum of pure and hybrid myosin heavy chain-based fibre types in rat skeletal muscle. Histochemistry 1993, 100, 149–153. [Google Scholar] [CrossRef]
  37. Schiaffino, S. Fibre types in skeletal muscle: A personal account. Acta Physiol. 2010, 199, 451–463. [Google Scholar] [CrossRef]
  38. Bottinelli, R.; Canepari, M.; Pellegrino, M.A.; Reggiani, C. Force-velocity properties of human skeletal muscle fibres: Myosin heavy chain isoform and temperature dependence. J. Physiol. 1996, 495, 573–586. [Google Scholar] [CrossRef]
  39. Ranatunga, K.W.; Thomas, P.E. Correlation between shortening velocity, force-velocity relation and histochemical fibre-type composition in rat muscles. J. Muscle Res. Cell Motil. 1990, 11, 240–250. [Google Scholar] [CrossRef]
  40. Edgerton, V.R.; Roy, R.R. Regulation of skeletal muscle fiber size, shape and function. J. Biomech. 1991, 24, 123–133. [Google Scholar] [CrossRef]
  41. Talmadge, R.J.; Roy, R.R.; Edgerton, V.R. Muscle fiber types and function. Curr. Opin. Rheumatol. 1993, 5, 695–705. [Google Scholar] [CrossRef] [PubMed]
  42. Resnicow, D.I.; Deacon, J.C.; Warrick, H.M.; Spudich, J.A.; Leinwand, L.A. Functional diversity among a family of human skeletal muscle myosin motors. Proc. Natl. Acad. Sci. USA 2010, 107, 1053–1058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  43. Reiser, P.J.; Moss, R.L.; Giulian, G.G.; Greaser, M.L. Shortening velocity in single fibers from adult rabbit soleus muscles is correlated with myosin heavy chain composition. J. Biol. Chem. 1985, 260, 9077–9080. [Google Scholar] [CrossRef]
  44. Armstrong, R.B.; Phelps, R.O. Muscle fiber type composition of the rat hindlimb. Am. J. Anat. 1984, 171, 259–272. [Google Scholar] [CrossRef] [PubMed]
  45. Bloemberg, D.; Quadrilatero, J. Rapid determination of myosin heavy chain expression in rat, mouse, and human skeletal muscle using multicolor immunofluorescence analysis. PLoS ONE 2012, 7, e35273. [Google Scholar] [CrossRef]
  46. Haddad, F.; Arnold, C.; Zeng, M.; Baldwin, K. Interaction of thyroid state and denervation on skeletal myosin heavy chain expression. Muscle Nerve 1997, 20, 1487–1496. [Google Scholar] [CrossRef]
  47. Drzymala-Celichowska, H.; Karolczak, J.; Redowicz, M.J.; Bukowska, D. The content of myosin heavy chains in hindlimb muscles of female and male rats. J. Physiol. Pharmacol. Off. J. Pol. Physiol. Soc. 2012, 63, 187–193. [Google Scholar]
  48. D’Amico, D.; Marino Gammazza, A.; Macaluso, F.; Paladino, L.; Scalia, F.; Spinoso, G.; Dimauro, I.; Caporossi, D.; Cappello, F.; Di Felice, V.; et al. Sex-based differences after a single bout of exercise on PGC1α isoforms in skeletal muscle: A pilot study. FASEB J. 2021, 35, e21328. [Google Scholar]
  49. Gouspillou, G.; Sgarioto, N.; Norris, B.; Barbat-Artigas, S.; Aubertin-Leheudre, M.; Morais, J.A.; Burelle, Y.; Taivassalo, T.; Hepple, R.T. The relationship between muscle fiber type-specific PGC-1alpha content and mitochondrial content varies between rodent models and humans. PLoS ONE 2014, 9, e103044. [Google Scholar] [CrossRef]
  50. Meissner, J.D.; Umeda, P.K.; Chang, K.C.; Gros, G.; Scheibe, R.J. Activation of the beta myosin heavy chain promoter by MEF-2D, MyoD, p300, and the calcineurin/NFATc1 pathway. J. Cell. Physiol. 2007, 211, 138–148. [Google Scholar] [CrossRef]
  51. Widrick, J.J.; Romatowski, J.G.; Bain, J.L.; Trappe, S.W.; Trappe, T.A.; Thompson, J.L.; Costill, D.L.; Riley, D.A.; Fitts, R.H. Effect of 17 days of bed rest on peak isometric force and unloaded shortening velocity of human soleus fibers. Am. J. Physiol. 1997, 273, C1690–C1699. [Google Scholar] [CrossRef] [PubMed]
  52. Widrick, J.J.; Knuth, S.T.; Norenberg, K.M.; Romatowski, J.G.; Bain, J.L.; Riley, D.A.; Karhanek, M.; Trappe, S.W.; Trappe, T.A.; Costill, D.L.; et al. Effect of a 17 day spaceflight on contractile properties of human soleus muscle fibres. J. Physiol. 1999, 516, 915–930. [Google Scholar] [CrossRef] [PubMed]
  53. Bottinelli, R.; Pellegrino, M.A.; Canepari, M.; Rossi, R.; Reggiani, C. Specific contributions of various muscle fibre types to human muscle performance: An in vitro study. J. Electromyogr. Kinesiol. Off. J. Int. Soc. Electrophysiol. Kinesiol. 1999, 9, 87–95. [Google Scholar] [CrossRef]
  54. Hikida, R.S.; Staron, R.S.; Hagerman, F.C.; Walsh, S.; Kaiser, E.; Shell, S.; Hervey, S. Effects of high-intensity resistance training on untrained older men. II. Muscle fiber characteristics and nucleo-cytoplasmic relationships. J. Gerontol. Ser. A Biol. Sci. Med Sci. 2000, 55, B347–B354. [Google Scholar] [CrossRef] [Green Version]
  55. Campos, G.E.; Luecke, T.J.; Wendeln, H.K.; Toma, K.; Hagerman, F.C.; Murray, T.F.; Ragg, K.E.; Ratamess, N.A.; Kraemer, W.J.; Staron, R.S. Muscular adaptations in response to three different resistance-training regimens: Specificity of repetition maximum training zones. Eur. J. Appl. Physiol. 2002, 88, 50–60. [Google Scholar] [CrossRef]
  56. Allen, D.L.; Harrison, B.C.; Maass, A.; Bell, M.L.; Byrnes, W.C.; Leinwand, L.A. Cardiac and skeletal muscle adaptations to voluntary wheel running in the mouse. J. Appl. Physiol. 2001, 90, 1900–1908. [Google Scholar] [CrossRef] [Green Version]
  57. Ausoni, S.; Gorza, L.; Schiaffino, S.; Gundersen, K.; Lomo, T. Expression of myosin heavy chain isoforms in stimulated fast and slow rat muscles. J. Neurosci. Off. J. Soc. Neurosci. 1990, 10, 153–160. [Google Scholar] [CrossRef] [Green Version]
  58. Liu, Y.; Schlumberger, A.; Wirth, K.; Schmidtbleicher, D.; Steinacker, J.M. Different effects on human skeletal myosin heavy chain isoform expression: Strength vs. combination training. J. Appl. Physiol. 2003, 94, 2282–2288. [Google Scholar] [CrossRef] [Green Version]
  59. Kesidis, N.; Metaxas, T.I.; Vrabas, I.S.; Stefanidis, P.; Vamvakoudis, E.; Christoulas, K.; Mandroukas, A.; Balasas, D.; Mandroukas, K. Myosin heavy chain isoform distribution in single fibres of bodybuilders. Eur. J. Appl. Physiol. 2008, 103, 579–583. [Google Scholar] [CrossRef]
  60. Staron, R.S. Correlation between myofibrillar ATPase activity and myosin heavy chain composition in single human muscle fibers. Histochemistry 1991, 96, 21–24. [Google Scholar] [CrossRef]
  61. Putman, C.T.; Xu, X.; Gillies, E.; MacLean, I.M.; Bell, G.J. Effects of strength, endurance and combined training on myosin heavy chain content and fibre-type distribution in humans. Eur. J. Appl. Physiol. 2004, 92, 376–384. [Google Scholar] [CrossRef] [PubMed]
  62. Mukherjee, K.; Conway de Macario, E.; Macario, A.J.; Brocchieri, L. Chaperonin genes on the rise: New divergent classes and intense duplication in human and other vertebrate genomes. BMC Evol. Biol. 2010, 1, 64. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  63. Caruso Bavisotto, C.; Alberti, G.; Vitale, A.M.; Paladino, L.; Campanella, C.; Rappa, F.; Gorska, M.; Conway de Macario, E.; Cappello, F.; Macario, A.J.L.; et al. Hsp60 Post-translational Modifications: Functional and Pathological Consequences. Front. Mol. Biosci. 2020, 7, 95. [Google Scholar] [CrossRef] [PubMed]
  64. Ishii, N. GroEL and the GroEL-GroES Complex. Sub Cell. Biochem. 2017, 83, 483–504. [Google Scholar]
  65. Vilasi, S.; Bulone, D.; Caruso Bavisotto, C.; Campanella, C.; Marino Gammazza, A.; San Biagio, P.L.; Cappello, F.; Conway de Macario, E.; Macario, A.J.L. Chaperonin of Group I: Oligomeric Spectrum and Biochemical and Biological Implications. Front. Mol. Biosci. 2017, 4, 99. [Google Scholar] [CrossRef]
  66. Horwich, A.L. Protein folding in the cell: An inside story. Nat. Med. 2011, 17, 1211–1216. [Google Scholar] [CrossRef]
  67. Henderson, B.; Fares, M.A.; Lund, P.A. Chaperonin 60: A paradoxical, evolutionarily conserved protein family with multiple moonlighting functions. Biol. Rev. Camb. Philos. Soc. 2013, 88, 955–987. [Google Scholar] [CrossRef]
  68. Nisemblat, S.; Parnas, A.; Yaniv, O.; Azem, A.; Frolow, F. Crystallization and structure determination of a symmetrical ‘football’ complex of the mammalian mitochondrial Hsp60-Hsp10 chaperonins. Acta Crystallogr. Sect. F Struct. Biol. Commun. 2014, 70, 116–119. [Google Scholar] [CrossRef] [Green Version]
  69. Viitanen, P.V.; Lorimer, G.H.; Seetharam, R.; Gupta, R.S.; Oppenheim, J.; Thomas, J.O.; Cowan, N.J. Mammalian mitochondrial chaperonin 60 functions as a single toroidal ring. J. Biol. Chem. 1992, 267, 695–698. [Google Scholar] [CrossRef]
  70. Vilasi, S.; Carrotta, R.; Mangione, M.R.; Campanella, C.; Librizzi, F.; Randazzo, L.; Martorana, V.; Marino Gammazza, A.; Ortore, M.G.; Vilasi, A.; et al. Human Hsp60 with its mitochondrial import signal occurs in solution as heptamers and tetradecamers remarkably stable over a wide range of concentrations. PLoS ONE 2014, 9, e97657. [Google Scholar] [CrossRef] [Green Version]
  71. Nielsen, K.L.; Cowan, N.J. A single ring is sufficient for productive chaperonin-mediated folding in vivo. Mol. Cell 1998, 2, 93–99. [Google Scholar] [CrossRef]
  72. Christensen, J.H.; Nielsen, M.N.; Hansen, J.; Fuchtbauer, A.; Fuchtbauer, E.M.; West, M.; Corydon, T.J.; Gregersen, N.; Bross, P. Inactivation of the hereditary spastic paraplegia-associated Hspd1 gene encoding the Hsp60 chaperone results in early embryonic lethality in mice. Cell Stress Chaperones 2010, 15, 851–863. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Berger, E.; Rath, E.; Yuan, D.; Waldschmitt, N.; Khaloian, S.; Allgauer, M.; Staszewski, O.; Lobner, E.M.; Schottl, T.; Giesbertz, P.; et al. Mitochondrial function controls intestinal epithelial stemness and proliferation. Nat. Commun. 2016, 7, 13171. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Tang, H.; Li, J.; Liu, X.; Wang, G.; Luo, M.; Deng, H. Down-regulation of HSP60 Suppresses the Proliferation of Glioblastoma Cells via the ROS/AMPK/mTOR Pathway. Sci. Rep. 2016, 6, 28388. [Google Scholar] [CrossRef] [Green Version]
  75. Cappello, F.; Marino Gammazza, A.; Palumbo Piccionello, A.; Campanella, C.; Pace, A.; Conway de Macario, E.; Macario, A.J. Hsp60 chaperonopathies and chaperonotherapy: Targets and agents. Expert Opin. Ther. Targets 2014, 18, 185–208. [Google Scholar] [CrossRef]
  76. Singh, B.; Patel, H.V.; Ridley, R.G.; Freeman, K.B.; Gupta, R.S. Mitochondrial import of the human chaperonin (HSP60) protein. Biochem. Biophys. Res. Commun. 1990, 169, 391–396. [Google Scholar] [CrossRef]
  77. Campanella, C.; Bucchieri, F.; Merendino, A.M.; Fucarino, A.; Burgio, G.; Corona, D.F.; Barbieri, G.; David, S.; Farina, F.; Zummo, G.; et al. The odyssey of Hsp60 from tumor cells to other destinations includes plasma membrane-associated stages and Golgi and exosomal protein-trafficking modalities. PLoS ONE 2012, 7, e42008. [Google Scholar] [CrossRef] [Green Version]
  78. Cappello, F.; Conway de Macario, E.; Marasa, L.; Zummo, G.; Macario, A.J. Hsp60 expression, new locations, functions and perspectives for cancer diagnosis and therapy. Cancer Biol. Ther. 2008, 7, 801–909. [Google Scholar] [CrossRef]
  79. Cheng, M.Y.; Hartl, F.U.; Martin, J.; Pollock, R.A.; Kalousek, F.; Neupert, W.; Hallberg, E.M.; Hallberg, R.L.; Horwich, A.L. Mitochondrial heat-shock protein hsp60 is essential for assembly of proteins imported into yeast mitochondria. Nature 1989, 337, 620–625. [Google Scholar] [CrossRef] [Green Version]
  80. Lin, Z.; Madan, D.; Rye, H.S. GroEL stimulates protein folding through forced unfolding. Nat. Struct. Mol. Biol. 2008, 15, 303–311. [Google Scholar] [CrossRef]
  81. Marino Gammazza, A.; Bavisotto, C.C.; Barone, R.; de Macario, E.C.; Macario, A.J. Alzheimer’s Disease and Molecular Chaperones: Current Knowledge and the Future of Chaperonotherapy. Curr. Pharm. Des. 2016, 22, 4040–4049. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  82. Kaufman, B.A.; Newman, S.M.; Hallberg, R.L.; Slaughter, C.A.; Perlman, P.S.; Butow, R.A. In organello formaldehyde crosslinking of proteins to mtDNA: Identification of bifunctional proteins. Proc. Natl. Acad. Sci. USA 2000, 97, 7772–7777. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  83. Kaufman, B.A.; Kolesar, J.E.; Perlman, P.S.; Butow, R.A. A function for the mitochondrial chaperonin Hsp60 in the structure and transmission of mitochondrial DNA nucleoids in Saccharomyces cerevisiae. J. Cell Biol. 2003, 163, 457–461. [Google Scholar] [CrossRef] [Green Version]
  84. Deocaris, C.C.; Kaul, S.C.; Wadhwa, R. On the brotherhood of the mitochondrial chaperones mortalin and heat shock protein 60. Cell Stress Chaperones 2006, 11, 116–128. [Google Scholar] [CrossRef]
  85. Sigal, L.H.; Williams, S.; Soltys, B.; Gupta, R. H9724, a monoclonal antibody to Borrelia burgdorferi’s flagellin, binds to heat shock protein 60 (HSP60) within live neuroblastoma cells: A potential role for HSP60 in peptide hormone signaling and in an autoimmune pathogenesis of the neuropathy of Lyme disease. Cell. Mol. Neurobiol. 2001, 21, 477–495. [Google Scholar] [PubMed]
  86. Chandra, D.; Choy, G.; Tang, D.G. Cytosolic accumulation of HSP60 during apoptosis with or without apparent mitochondrial release: Evidence that its pro-apoptotic or pro-survival functions involve differential interactions with caspase-3. J. Biol. Chem. 2007, 282, 31289–31301. [Google Scholar] [CrossRef] [Green Version]
  87. Cappello, F.; Bellafiore, M.; Palma, A.; David, S.; Marciano, V.; Bartolotta, T.; Sciume, C.; Modica, G.; Farina, F.; Zummo, G.; et al. 60KDa chaperonin (HSP60) is over-expressed during colorectal carcinogenesis. Eur. J. Histochem. 2003, 47, 105–110. [Google Scholar] [CrossRef]
  88. Cappello, F.; David, S.; Rappa, F.; Bucchieri, F.; Marasa, L.; Bartolotta, T.E.; Farina, F.; Zummo, G. The expression of HSP60 and HSP10 in large bowel carcinomas with lymph node metastase. BMC Cancer 2005, 5, 139. [Google Scholar] [CrossRef] [Green Version]
  89. Caruso Bavisotto, C.; Cipolla, C.; Graceffa, G.; Barone, R.; Bucchieri, F.; Bulone, D.; Cabibi, D.; Campanella, C.; Marino Gammazza, A.; Pitruzzella, A.; et al. Immunomorphological Pattern of Molecular Chaperones in Normal and Pathological Thyroid Tissues and Circulating Exosomes: Potential Use in Clinics. Int. J. Mol. Sci. 2019, 20, 4496. [Google Scholar] [CrossRef] [Green Version]
  90. Faried, A.; Sohda, M.; Nakajima, M.; Miyazaki, T.; Kato, H.; Kuwano, H. Expression of heat-shock protein Hsp60 correlated with the apoptotic index and patient prognosis in human oesophageal squamous cell carcinoma. Eur. J. Cancer 2004, 40, 2804–2811. [Google Scholar] [CrossRef]
  91. Dubin, R.A.; Ally, A.H.; Chung, S.; Piatigorsky, J. Human alpha B-crystallin gene and preferential promoter function in lens. Genomics 1990, 7, 594–601. [Google Scholar] [CrossRef]
  92. Kappé, G.; Franck, E.; Verschuure, P.; Boelens, W.C.; Leunissen, J.A.; de Jong, W.W. The human genome encodes 10 alpha-crystallin-related small heat shock proteins: HspB1-10. Cell Stress Chaperones 2003, 8, 53–61. [Google Scholar] [CrossRef]
  93. Kriehuber, T.; Rattei, T.; Weinmaier, T.; Bepperling, A.; Haslbeck, M.; Buchner, J. Independent evolution of the core domain and its flanking sequences in small heat shock proteins. FASEB J. 2010, 24, 3633–3642. [Google Scholar] [CrossRef] [PubMed]
  94. Fichna, J.P.; Potulska-Chromik, A.; Miszta, P.; Redowicz, M.J.; Kaminska, A.M.; Zekanowski, C.; Filipek, S. A novel dominant D109A CRYAB mutation in a family with myofibrillar myopathy affects αB-crystallin structure. BBA Clin. 2016, 11, 1–7. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Sacconi, S.; Féasson, L.; Antoine, J.C.; Pécheux, C.; Bernard, R.; Cobo, A.M.; Casarin, A.; Salviati, L.; Desnuelle, C.; Urtizberea, A. A novel CRYAB mutation resulting in multisystemic disease. Neuromuscul. Disord. 2012, 22, 66–72. [Google Scholar] [CrossRef]
  96. Vicart, P.; Caron, A.; Guicheney, P.; Li, Z.; Prévost, M.C.; Faure, A.; Chateau, D.; Chapon, F.; Tomé, F.; Dupret, J.M.; et al. A missense mutation in the alphaB-crystallin chaperone gene causes a desmin-related myopathy. Nat. Genet. 1998, 20, 92–95. [Google Scholar] [CrossRef]
  97. Del Bigio, M.R.; Chudley, A.E.; Sarnat, H.B.; Campbell, C.; Goobie, S.; Chodirker, B.N.; Selcen, D. Infantile muscular dystrophy in Canadian aboriginals is an αB-crystallinopathy. Ann. Neurol. 2011, 69, 866–871. [Google Scholar] [CrossRef] [Green Version]
  98. Inagaki, N.; Hayashi, T.; Arimura, T.; Koga, Y.; Takahashi, M.; Shibata, H.; Teraoka, K.; Chikamori, T.; Yamashina, A.; Kimura, A. Alpha B-crystallin mutation in dilated cardiomyopathy. Biochem. Biophys Res. Commun. 2006, 7, 379–386. [Google Scholar] [CrossRef]
  99. Pilotto, A.; Marziliano, N.; Pasotti, M.; Grasso, M.; Costante, A.M.; Arbustini, E. alphaB-crystallin mutation in dilated cardiomyopathies: Low prevalence in a consecutive series of 200 unrelated probands. Biochem. Biophys Res. Commun. 2006, 346, 1115–1117. [Google Scholar] [CrossRef]
  100. Reilich, P.; Schoser, B.; Schramm, N.; Krause, S.; Schessl, J.; Kress, W.; Müller-Höcker, J.; Walter, M.C.; Lochmuller, H. The p.G154S mutation of the alpha-B crystallin gene (CRYAB) causes late-onset distal myopathy. Neuromuscul. Disord. 2010, 20, 255–259. [Google Scholar] [CrossRef]
  101. Selcen, D.; Engel, A.G. Myofibrillar myopathy caused by novel dominant negative alpha B-crystallin mutations. Ann. Neurol. 2003, 54, 804–810. [Google Scholar] [CrossRef] [PubMed]
  102. Jehle, S.; Vollmar, B.S.; Bardiaux, B.; Dove, K.K.; Rajagopal, P.; Gonen, T.; Oschkinat, H.; Klevit, R.E. N-terminal domain of alphaB-crystallin provides a conformational switch for multimerization and structural heterogeneity. Proc. Natl. Acad. Sci. USA 2011, 108, 6409–6414. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  103. Zantema, A.; Verlaan-De Vries, M.; Maasdam, D.; Bol, S.; van der Eb, A. Heat shock protein 27 and alpha B-crystallin can form a complex, which dissociates by heat shock. J. Biol. Chem. 1992, 25, 12936–12941. [Google Scholar] [CrossRef]
  104. Fontaine, J.M.; Sun, X.; Benndorf, R.; Welsh, M.J. Interactions of HSP22 (HSPB8) with HSP20, alphaB-crystallin, and HSPB3. Biochem. Biophys Res. Commun. 2005, 337, 1006–1011. [Google Scholar] [CrossRef]
  105. Eaton, P.; Fuller, W.; Bell, J.R.; Shattock, M.J. AlphaB crystallin translocation and phosphorylation: Signal transduction pathways and preconditioning in the isolated rat heart. J. Mol. Cell Cardiol. 2001, 33, 1659–1671. [Google Scholar] [CrossRef]
  106. Ito, H.; Okamoto, K.; Nakayama, H.; Isobe, T.; Kato, K. Phosphorylation of alphaB-crystallin in response to various types of stress. J. Biol. Chem. 1997, 272, 29934–29941. [Google Scholar] [CrossRef] [Green Version]
  107. Bakthisaran, R.; Tangirala, R.; Rao, C.M. Small heat shock proteins: Role in cellular functions and pathology. Biochim. Biophys Acta 2015, 1854, 291–319. [Google Scholar] [CrossRef] [Green Version]
  108. Kato, K.; Ito, H.; Kamei, K.; Inaguma, Y.; Iwamoto, I.; Saga, S. Phosphorylation of alpha beta-crystallin in mitotic cells and identification enzymatic activities responsible for phosphorylation. J. Biol. Chem. 1998, 273, 28346–28354. [Google Scholar] [CrossRef] [Green Version]
  109. Nicholl, I.D.; Quinlan, R.A. Chaperone activity of alpha-crystallins modulates intermediate filament assembly. EMBO J. 1994, 13, 945–953. [Google Scholar] [CrossRef]
  110. Fittipaldi, S.; Mercatelli, N.; Dimauro, I.; Jackson, M.J.; Paronetto, M.P.; Caporossi, D. Alpha B-crystallin induction in skeletal muscle cells under redox imbalance is mediated by a JNK-dependent regulatory mechanism. Free Radic. Biol. Med. 2015, 86, 331–342. [Google Scholar] [CrossRef]
  111. Morrison, L.E.; Hoover, H.E.; Thuerauf, D.J.; Glembotski, C.C. Mimicking phosphorylation of αB-Crystallin on Serine-59 is necessary and sufficient to provide maximal protection of cardiac myocytes from apoptosis. Circ. Res. 2003, 92, 203–211. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  112. Morrison, L.E.; Whittaker, R.J.; Klepper, R.E.; Wawrousek, E.F.; Glembotski, C.C. Roles for alphaB-crystallin and HSPB2 in protecting the myocardium from ischemia-reperfusion-induced damage in a KO mouse model. Am. J. Physiol. Heart Circ. Physiol. 2004, 286, 847–855. [Google Scholar] [CrossRef] [PubMed]
  113. Reddy, V.S.; Jakhotia, S.; Reddy, P.Y.; Reddy, G.B. Hyperglycemia induced expression, phosphorylation, and translocation of αB-crystallin in rat skeletal muscle. IUBMB Life 2015, 67, 291–299. [Google Scholar] [CrossRef] [PubMed]
  114. Den Engelsman, J.; Gerrits, D.; de Jong, W.W.; Robbins, J.; Kato, K.; Boelens, W.C. Nuclear import of {alpha}B-crystallin is phosphorylation-dependent and hampered by hyperphosphorylation of the myopathy-related mutant R120G. J. Biol. Chem. 2005, 280, 37139–37148. [Google Scholar] [CrossRef] [Green Version]
  115. Launay, N.; Goudeau, B.; Kato, K.; Vicart, P.; Lilienbaum, A. Cell signaling pathways to alphaB-crystallin following stresses of the cytoskeleton. Expt. Cell Res. 2006, 312, 3570–3584. [Google Scholar] [CrossRef]
  116. Antonioni, A.; Dimauro, I.; Fantini, C.; Barone, R.; Macaluso, F.; Di Felice, V.; Caporossi, D. αB-crystallin response to a pro-oxidant non-cytotoxic environment in murine cardiac cells: An “in vitro” and “in vivo” study. Free Radic. Biol. Med. 2020, 152, 301–312. [Google Scholar] [CrossRef]
  117. Aggeli, I.K.; Beis, I.; Gaitanaki, C. Oxidative stress and calpain inhibition induce alpha B-crystallin phosphorylation via p38-MAPK and calcium signalling pathways in H9c2 cells. Cell. Signal. 2008, 20, 1292–1302. [Google Scholar] [CrossRef]
  118. Beltran Valls, M.R.; Wilkinson, D.J.; Narici, M.V.; Smith, K.; Phillips, B.E.; Caporossi, D.; Atherton, P.J. Protein carbonylation and heat shock proteins in human skeletal muscle: Relationships to age and sarcopenia. J. Gerontol. A Biol. Sci. Med. Sci. 2015, 70, 174–181. [Google Scholar] [CrossRef] [Green Version]
  119. Ivanov, O.; Chen, F.; Wiley, E.L.; Keswani, A.; Diaz, L.K.; Memmel, H.C.; Rademaker, A.; Gradishar, W.J.; Morrow, M.; Khan, S.A.; et al. alphaB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer. Breast Cancer Res. Treat. 2008, 111, 411–417. [Google Scholar] [CrossRef]
  120. Neppl, R.L.; Kataoka, M.; Wang, D.Z. Crystallin-αB regulates skeletal muscle homeostasis via modulation of argonaute2 activity. J. Biol. Chem. 2014, 289, 17240–17248. [Google Scholar] [CrossRef] [Green Version]
  121. Magi, F.; Dimauro, I.; Margheritini, F.; Duranti, G.; Mercatelli, N.; Fantini, C.; Ripani, F.R.; Sabatini, S.; Caporossi, D. Telomere length is independently associated with age, oxidative biomarkers, and sport training in skeletal muscle of healthy adult males. Free Radic. Res. 2018, 52, 639–647. [Google Scholar] [CrossRef] [PubMed]
  122. Pereira, M.B.; Santos, A.M.; Gonçalves, D.C.; Cardoso, A.C.; Consonni, S.R.; Gozzo, F.C.; Oliveira, P.S.; Pereira, A.H.; Figueiredo, A.R.; Tiroli-Cepeda, A.O.; et al. Corrigendum: αB-crystallin interacts with and prevents stress-activated proteolysis of focal adhesion kinase by calpain in cardiomyocytes. Nat. Commun. 2015, 23, 6508. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  123. Koteiche, H.A.; McHaourab, H.S. Mechanism of chaperone function in small heat shock proteins. Phosphorylation-induced activation of two modes binding in alphaB-crystallin. J. Biol. Chem. 2003, 278, 10361–10367. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  124. Caporossi, D.; Parisi, A.; Fantini, C.; Grazioli, E.; Cerulli, C.; Dimauro, I. AlphaB-crystallin and breast cancer: Role and possible therapeutic strategies. Cell Stress Chaperones 2020. [Google Scholar] [CrossRef]
  125. Richter, K.; Haslbeck, M.; Buchner, J. The heat shock response: Life on the verge of death. Mol. Cell 2010, 22, 253–266. [Google Scholar] [CrossRef]
  126. Bhat, S.P.; Nagineni, C.N. αB subunit of lens-specific protein α-crystallin is present in other ocular and non-ocular tissue. Biochem. Biophys. Res. Commun. 1989, 158, 319–325. [Google Scholar] [CrossRef]
  127. Bornman, L.; Polla, B.S.; Lotz, B.P.; Gericke, G.S. Expression of heat-shock/stress proteins in Duchenne muscular dystrophy. Muscle Nerve 1995, 18, 23–31. [Google Scholar] [CrossRef]
  128. Morton, J.P.; Maclaren, D.P.; Cable, N.T.; Campbell, I.T.; Evans, L.; Kayani, A.C.; McArdle, A.; Drust, B. Trained men display increased basal heat shock protein content of skeletal muscle. Med. Sci. Sports Exerc. 2008, 40, 1255–1262. [Google Scholar] [CrossRef]
  129. Folkesson, M.; Mackey, A.L.; Langberg, H.; Oskarsson, E.; Piehl-Aulin, K.; Henriksson, J.; Kadi, F. The expression of heat shock protein in human skeletal muscle: Effects of muscle fibre phenotype and training background. Acta Physiol. 2013, 209, 26–33. [Google Scholar] [CrossRef]
  130. Ogata, T.; Oishi, Y.; Higashida, K.; Higuchi, M.; Muraoka, I. Prolonged exercise training induces long-term enhancement of HSP70 expression in rat plantaris muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2009, 296, R1557–R1563. [Google Scholar] [CrossRef]
  131. Moura, C.S.; Lollo, P.C.; Morato, P.N.; Nisishima, L.H.; Carneiro, E.M.; Amaya-Farfan, J. Whey protein hydrolysate enhances HSP90 but does not alter HSP60 and HSP25 in skeletal muscle of rats. PLoS ONE 2014, 9, e83437. [Google Scholar] [CrossRef]
  132. Mattson, J.P.; Ross, C.R.; Kilgore, J.L.; Musch, T.I. Induction of mitochondrial stress proteins following treadmill running. Med. Sci. Sports Exerc. 2000, 32, 365–369. [Google Scholar] [CrossRef] [PubMed]
  133. Samelman, T.R. Heat shock protein expression is increased in cardiac and skeletal muscles of Fischer 344 rats after endurance training. Exp. Physiol. 2000, 85, 92–102. [Google Scholar] [CrossRef] [PubMed]
  134. Barone, R.; Macaluso, F.; Sangiorgi, C.; Campanella, C.; Marino Gammazza, A.; Moresi, V.; Coletti, D.; Conway de Macario, E.; Macario, A.J.; Cappello, F.; et al. Skeletal muscle Heat shock protein 60 increases after endurance training and induces peroxisome proliferator-activated receptor gamma coactivator 1 alpha1 expression. Sci. Rep. 2016, 6, 19781. [Google Scholar] [CrossRef] [Green Version]
  135. Barone, R.; Sangiorgi, C.; Marino Gammazza, A.; D’Amico, D.; Salerno, M.; Cappello, F.; Pomara, C.; Zummo, G.; Farina, F.; Di Felice, V.; et al. Effects of Conjugated Linoleic Acid Associated with Endurance Exercise on Muscle Fibres and Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1 alpha Isoforms. J. Cell. Physiol. 2017, 232, 1086–1094. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  136. Hood, D.A.; Takahashi, M.; Connor, M.K.; Freyssenet, D. Assembly of the cellular powerhouse: Current issues in muscle mitochondrial biogenesis. Exerc. Sport Sci. Rev. 2000, 28, 68–73. [Google Scholar]
  137. Collier, M.P.; Benesch, J.L.P. Small heat-shock proteins and their role in mechanical stress. Cell Stress Chaperones 2020, 25, 601–613. [Google Scholar] [CrossRef] [Green Version]
  138. Dimauro, I.; Scalabrin, M.; Fantini, C.; Grazioli, E.; Beltran Valls, M.R.; Mercatelli, N.; Parisi, A.; Sabatini, S.; Di Luigi, L.; Caporossi, D. Resistance training and redox homeostasis: Correlation with age-associated genomic changes. Redox Biol. 2016, 10, 34–44. [Google Scholar] [CrossRef] [Green Version]
  139. Mercatelli, N.; Dimauro, I.; Ciafré, S.A.; Farace, M.G.; Caporossi, D. AlphaB-crystallin is involved in oxidative stress protection determined by VEGF in skeletal myoblasts. Free Radic. Biol. Med. 2010, 49, 374–382. [Google Scholar] [CrossRef]
  140. Karin, M.; Lin, A. NF-kappaB at the crossroads of life and death. Nat. Immunol. 2002, 3, 221–227. [Google Scholar] [CrossRef]
  141. Perkins, N.D.; Gilmore, T.D. Good cop, bad cop: The different faces of NF-kappaB. Cell Death Differ. 2006, 13, 759–772. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  142. Li, D.W.; Liu, J.P.; Mao, Y.W.; Xiang, H.; Wang, J.; Ma, W.Y.; Dong, Z.; Pike, H.M.; Brown, R.E.; Reed, J.C. Calcium-activated RAF/MEK/ERK signaling pathway mediates p53-dependent apoptosis and is abrogated by alpha B-crystallin through inhibition of RAS activation. Mol. Biol. Cell 2005, 16, 4437–4453. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  143. Mao, Y.W.; Liu, J.P.; Xiang, H.; Li, D.W. Human alphaA- and alphaB-crystallins bind to Bax and Bcl-X(S) to sequester their translocation during staurosporine-induced apoptosis. Cell Death Differ. 2004, 11, 512–526. [Google Scholar] [CrossRef] [PubMed]
  144. Liu, S.; Li, J.; Tao, Y.; Xiao, X. Small heat shock protein alphaB-crystallin binds to p53 to sequester its translocation to mitochondria during hydrogen peroxide-induced apoptosis. Biochem. Biophys. Res. Commun. 2007, 354, 109–114. [Google Scholar] [CrossRef] [PubMed]
  145. Kamradt, M.C.; Chen, F.; Cryns, V.L. The small heat shock protein alpha B-crystallin negatively regulates cytochrome c- and caspase-8-dependent activation of caspase-3 by inhibiting its autoproteolytic maturation. J. Biol. Chem. 2001, 276, 16059–16063. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  146. Bartel, D.P. MicroRNAs: Genomics, biogenesis, mechanism, and function. Cell 2004, 116, 281–297. [Google Scholar] [CrossRef] [Green Version]
  147. Djuranovic, S.; Nahvi, A.; Green, R. A parsimonious model for gene regulation by miRNAs. Science 2011, 331, 550–553. [Google Scholar] [CrossRef] [Green Version]
  148. Iwaki, T.; Iwaki, A.; Liem, R.K.; Goldman, J.E. Expression of alpha B-crystallin in the developing rat kidney. Kidney Int. 1991, 40, 52–56. [Google Scholar] [CrossRef] [Green Version]
  149. Lowe, J.; McDermott, H.; Pike, I.; Spendlove, I.; Landon, M.; Mayer, R.J. alpha B crystallin expression in non-lenticular tissues and selective presence in ubiquitinated inclusion bodies in human disease. J. Pathol. 1992, 166, 61–68. [Google Scholar] [CrossRef]
  150. Larkins, N.T.; Murphy, R.M.; Lamb, G.D. Absolute amounts and diffusibility of HSP72, HSP25, and _B-crystallin in fast- and slow-twitch skeletal muscle fibers of rat. Am. J. Physiol. Cell Physiol. 2012, 302, 228–239. [Google Scholar] [CrossRef]
  151. Larkins, N.T.; Murphy, R.M.; Lamb, G.D. Influences of temperature, oxidative stress, and phosphorylation on binding of heat shock proteins in skeletal muscle fibers. Am. J. Physiol. Cell Physiol. 2012, 303, 654–665. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  152. Frankenberg, N.T.; Lamb, G.D.; Overgaard, K.; Murphy, R.M.; Vissing, K. Small heat shock proteins translocate to the cytoskeleton in human skeletal muscle following eccentric exercise independently of phosphorylation. J. Appl. Physiol. (1985) 2014, 116, 1463–1472. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  153. Paulsen, G.; Lauritzen, F.; Bayer, M.L.; Kalhovde, J.M.; Ugelstad, I.; Owe, S.G.; Hallén, J.; Bergersen, L.H.; Raastad, T. Subcellular movement and expression of HSP27, alphaB-crystallin, and HSP70 after two bouts of eccentric exercise in humans. J. Appl. Physiol. (1985) 2009, 107, 570–582. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  154. Féasson, L.; Stockholm, D.; Freyssenet, D.; Richard, I.; Duguez, S.; Beckmann, J.S.; Denis, C. Molecular adaptations of neuromuscular disease-associated proteins in response to eccentric exercise in human skeletal muscle. J. Physiol. 2002, 543, 297–306. [Google Scholar] [CrossRef] [PubMed]
  155. Koh, T.J.; Escobedo, J. Cytoskeletal disruption and small heat shock protein translocation immediately after lengthening contractions. Am. J. Physiol. Cell Physiol. 2004, 286, 713–722. [Google Scholar] [CrossRef]
  156. Jacko, D.; Bersiner, K.; Hebchen, J.; de Marées, M.; Bloch, W.; Gehlert, S. Phosphorylation of αB-crystallin and its cytoskeleton association differs in skeletal myofiber types depending on resistance exercise intensity and volume. J. Appl. Physiol. (1985) 2019, 126, 1607–1618. [Google Scholar] [CrossRef]
  157. Neufer, P.D.; Benjamin, I.J. Differential expression of B-crystallin and Hsp27 in skeletal muscle during continuous contractile activity. Relationship to myogenic regulatory factors. J. Biol. Chem. 1996, 271, 24089–24095. [Google Scholar] [CrossRef] [Green Version]
  158. Atomi, Y.; Toro, K.; Masuda, T.; Hatta, H. Fibertype-specific alphaB-crystallin distribution and its shifts with T(3) and PTU treatments in rat hindlimb muscles. J. Appl. Physiol. 2000, 88, 1355–1364. [Google Scholar] [CrossRef] [Green Version]
  159. Warburton, D.E.R.; Bredin, S.S.D. Health benefits of physical activity: A systematic review of current systematic reviews. Curr. Opin. Cardiol. 2017, 32, 541–556. [Google Scholar] [CrossRef]
  160. Cartee, G.D.; Hepple, R.T.; Bamman, M.M.; Zierath, J.R. Exercise Promotes Healthy Aging of Skeletal Muscle. Cell Metab. 2016, 23, 1034–1047. [Google Scholar] [CrossRef] [Green Version]
  161. Grazioli, E.; Dimauro, I.; Mercatelli, N.; Wang, G.; Pitsiladis, Y.; Di Luigi, L.; Caporossi, D. Physical activity in the prevention of human diseases: Role of epigenetic modifications. BMC Genom. 2017, 14, 802. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  162. Busquets-Cortés, C.; Capó, X.; Bibiloni, M.D.M.; Martorell, M.; Ferrer, M.D.; Argelich, E.; Bouzas, C.; Carreres, S.; Tur, J.A.; Pons, A.; et al. Peripheral Blood Mononuclear Cells Antioxidant Adaptations to Regular Physical Activity in Elderly People. Nutrients 2018, 10, 1555. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  163. Ceci, R.; Beltran Valls, M.R.; Duranti, G.; Dimauro, I.; Quaranta, F.; Pittaluga, M.; Sabatini, S.; Caserotti, P.; Parisi, P.; Parisi, A.; et al. Oxidative stress responses to a graded maximal exercise test in older adults following explosive-type resistance training. Redox Biol. 2014, 2, 65–72. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  164. Ceci, R.; Duranti, G.; Di Filippo, E.S.; Bondi, D.; Verratti, V.; Doria, C.; Caporossi, D.; Sabatini, S.; Dimauro, I.; Pietrangelo, T. Corrigendum to “Endurance training improves plasma superoxide dismutase activity in healthy elderly” [Mechanisms of Ageing and Development 185 (2020) 111190]. Mech. Ageing Dev. 2020, 186, 111214. [Google Scholar] [CrossRef]
  165. Dimauro, I.; Sgura, A.; Pittaluga, M.; Magi, F.; Fantini, C.; Mancinelli, R.; Sgadari, A.; Fulle, S.; Caporossi, D. Regular exercise participation improves genomic stability in diabetic patients: An exploratory study to analyse telomere length and DNA damage. Sci. Rep. 2017, 7, 4137. [Google Scholar] [CrossRef] [Green Version]
  166. Pittaluga, M.; Sgadari, A.; Dimauro, I.; Tavazzi, B.; Parisi, P.; Caporossi, D. Physical exercise and redox balance in type 2 diabetics: Effects of moderate training on biomarkers of oxidative stress and DNA damage evaluated through comet assay. Oxidative. Med. Cell Longev. 2015, 2015, 981242. [Google Scholar] [CrossRef]
  167. Beltran Valls, M.R.; Dimauro, I.; Brunelli, A.; Tranchita, E.; Ciminelli, E.; Caserotti, P.; Duranti, G.; Sabatini, S.; Parisi, P.; Parisi, A.; et al. Explosive type of moderate-resistance training induces functional, cardiovascular, and molecular adaptations in the elderly. Age (Dordr) 2014, 36, 759–772. [Google Scholar] [CrossRef]
  168. Ahmed, H.M.; Blaha, M.J.; Nasir, K.; Rivera, J.J.; Blumenthal, R.S. Effects of physical activity on cardiovascular disease. Am. J. Cardiol. 2012, 109, 288–295. [Google Scholar] [CrossRef]
  169. Iwaki, T.; Iwaki, A.; Goldman, J.E. Alpha B-crystallin in oxidative muscle fibers and its accumulation in ragged-red fibers: A comparative immunohistochemical and histochemical study in human skeletal muscle. Acta Neuropathol. 1993, 85, 475–480. [Google Scholar] [CrossRef]
Table
Table 1. Fiber-type distribution and mitochondrial content in different skeletal muscles.
Table 1. Fiber-type distribution and mitochondrial content in different skeletal muscles.
Skeletal Muscles SpeciesGenderMain Fiber-Types %Mitochondrial ContentReferences
Vastus LateralisHumanMaleI 49–IIa 42%I > IIa > IIx [44,48]
PlantarisRatMaleIIx 45–IIa 21%IIa > I > IIx > IIb[44,48]
PlantarisRatFemaleIIb 46–IIx 40% [45]
SoleusRatMaleI 97%IIa > I > IIx > IIb [44,48]
SoleusRatFemaleI 99% [46]
GastrocnemiusRatMaleIIx 43–IIb 26% [44]
SoleusMouseMaleIIa 49–I 31% [44]
SoleusMouseFemaleI 49–IIa 35% [47]
EDLMouseMaleIIb 63–IIx 18% [47]
EDLMouseFemaleIIx 37–IIb 35% [47]
GastrocnemiusMouseMaleIIb 56–IIa 21%IIa > IIx > I > IIb [44,48]
EDL, extensor digitorum longus; I, type I; IIa, type IIa; IIx, type IIx; IIb, type IIb.
Table
Table 2. Hsp60 expression levels in different skeletal muscles after physical exercise.
Table 2. Hsp60 expression levels in different skeletal muscles after physical exercise.
Species/StrainGender (Age)Skeletal MusclesProtocol TrainingHsp60 LevelsReferences
HumanMale (28 ± 6 yrs)Vastus LateralisEndurance↑[128]
HumanMale (28 ± 6 yrs)Vastus LateralisAcute exercise=[128]
Rat/WistarMale (4 months)PlantarisEndurance=[130]
Rat/WistarFemale (ns)PlantarisEndurance↑[133]
Rat/Fischer 344Male (10 months)SoleusEndurance↑[133]
Rat/WistarFemale (ns)SoleusEndurance=[132]
Rat/WistarMale (ns)GastrocnemiusEndurance=[131]
Rat/Fischer 344Male (10 months)GastrocnemiusEndurance=[133]
Mouse/BALB/cMale (7 weeks)SoleusEndurance↑[134]
Mouse/BALB/cMale (12 weeks)SoleusAcute exercise↑[48]
Mouse/BALB/cFemale (12 weeks)SoleusAcute exercise=[48]
Mouse/BALB/cMale (12 weeks)EDLAcute exercise=[48]
Mouse/BALB/cFemale (12 weeks)EDLAcute exercise↑[48]
Mouse/BALB/cMale (7 weeks)GastrocnemiusEndurance=[134]
Hsp60, heat shock protein 60; EDL, extensor digitorum longus; arrow, increased levels of Hsp60; =, no difference; ns, not specified; yrs, years.
Table
Table 3. CRYAB expression levels in different skeletal muscles after physical exercise.
Table 3. CRYAB expression levels in different skeletal muscles after physical exercise.
Species/StrainGender (Age)Skeletal MusclesProtocol TrainingCRYAB Levels
(Protein) 		CRYAB (S59) LevelsReferences
HumanMale (25 ± 6 years)Vastus LateralisResistance↑NA[129]
Endurance=NA
HumanMale/Female
(21–37 years)		Biceps brachiiEndurance↑NA[153]
HumanMale
(20.3 ± 0.8 years)		Vastus LateralisEndurance↑NA[154]
HumanMale (24 ± 4 years)Vastus LateralisEndurance=NA[21]
HumanMale (24 ± 3 years)Vastus LateralisEndurance=↑[152]
HumanMale
(24.8 ± 3.8 years)		Vastus LateralisResistance=↑[156]
Mouse/BALB/cMale (7 weeks)Soleus Red GastrocnemiusEndurance=↑[32]
Mouse/C57BL/6Male (3 months)EDLResistance=↑[155]
CRYAB, αB-crystallin; CRYAB(S59), phospho-αBcrystallin (S59); EDL, extensor digitorum longus; arrow, increased levels of CRYAB/CRYAB(S59); =, no difference; NA, not applicable; yrs, years.
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Share and Cite

MDPI and ACS Style

D’Amico, D.; Fiore, R.; Caporossi, D.; Di Felice, V.; Cappello, F.; Dimauro, I.; Barone, R. Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise. Biology 2021, 10, 77. https://doi.org/10.3390/biology10020077

AMA Style

D’Amico D, Fiore R, Caporossi D, Di Felice V, Cappello F, Dimauro I, Barone R. Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise. Biology. 2021; 10(2):77. https://doi.org/10.3390/biology10020077

Chicago/Turabian Style

D’Amico, Daniela, Roberto Fiore, Daniela Caporossi, Valentina Di Felice, Francesco Cappello, Ivan Dimauro, and Rosario Barone. 2021. "Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise" Biology 10, no. 2: 77. https://doi.org/10.3390/biology10020077

APA Style

D’Amico, D., Fiore, R., Caporossi, D., Di Felice, V., Cappello, F., Dimauro, I., & Barone, R. (2021). Function and Fiber-Type Specific Distribution of Hsp60 and αB-Crystallin in Skeletal Muscles: Role of Physical Exercise. Biology, 10(2), 77. https://doi.org/10.3390/biology10020077

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop