International Journal of Molecular Sciences

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16 pages, 7137 KiB

Open AccessArticle

Apicobasal Surfaceome Architecture Encodes for Polarized Epithelial Functionality and Depends on Tumor Suppressor PTEN

by Anika Koetemann and Bernd Wollscheid

Int. J. Mol. Sci. 2022, 23(24), 16193; https://doi.org/10.3390/ijms232416193 - 19 Dec 2022

Cited by 2 | Viewed by 2083

Abstract

The loss of apicobasal polarity during the epithelial-to-mesenchymal transition (EMT) is a hallmark of cancer and metastasis. The key feature of this polarity in epithelial cells is the subdivision of the plasma membrane into apical and basolateral domains, with each orchestrating specific intra- [...] Read more.

The loss of apicobasal polarity during the epithelial-to-mesenchymal transition (EMT) is a hallmark of cancer and metastasis. The key feature of this polarity in epithelial cells is the subdivision of the plasma membrane into apical and basolateral domains, with each orchestrating specific intra- and extracellular functions. Epithelial transport and signaling capacities are thought to be determined largely by the quality, quantity, and nanoscale organization of proteins residing in these membrane domains, the apicobasal surfaceomes. Despite its implications for cancer, drug uptake, and infection, our current knowledge of how the polarized surfaceome is organized and maintained is limited. Here, we used chemoproteomic surfaceome scanning to establish proteotype maps of apicobasal surfaceomes and reveal quantitative distributions of, i.e., surface proteases, phosphatases, and tetraspanins as potential key regulators of polarized cell functionality. We show further that the tumor suppressor PTEN regulates polarized surfaceome architecture and uncover a potential role in collective cell migration. Our differential surfaceome analysis provides a molecular framework to elucidate polarized protein networks regulating epithelial functions and PTEN-associated cancer progression. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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16 pages, 3504 KiB

Open AccessArticle

Fluoxetine Enhances Synaptic Vesicle Trafficking and Energy Metabolism in the Hippocampus of Socially Isolated Rats

by Dragana Filipović, Victor Costina, Peter Findeisen and Dragos Inta

Int. J. Mol. Sci. 2022, 23(23), 15351; https://doi.org/10.3390/ijms232315351 - 5 Dec 2022

Cited by 5 | Viewed by 2150

Abstract

Chronic social isolation (CSIS)–induced alternation in synaptic and mitochondrial function of specific brain regions is associated with major depressive disorder (MDD). Despite the wide number of available medications, treating MDD remains an important challenge. Although fluoxetine (Flx) is the most frequently prescribed antidepressant, [...] Read more.

Chronic social isolation (CSIS)–induced alternation in synaptic and mitochondrial function of specific brain regions is associated with major depressive disorder (MDD). Despite the wide number of available medications, treating MDD remains an important challenge. Although fluoxetine (Flx) is the most frequently prescribed antidepressant, its mode of action is still unknown. To delineate affected molecular pathways of depressive-like behavior and identify potential targets upon Flx treatment, we performed a comparative proteomic analysis of hippocampal purified synaptic terminals (synaptosomes) of rats exposed to six weeks of CSIS, an animal model of depression, and/or followed by Flx treatment (lasting three weeks of six-week CSIS) to explore synaptic protein profile changes. Results showed that Flx in controls mainly induced decreased expression of proteins involved in energy metabolism and the redox system. CSIS led to increased expression of proteins that mainly participate in Ca²⁺/calmodulin-dependent protein kinase II (Camk2)-related neurotransmission, vesicle transport, and ubiquitination. Flx treatment of CSIS rats predominantly increased expression of proteins involved in synaptic vesicle trafficking (exocytosis and endocytosis), and energy metabolism (glycolytic and mitochondrial respiration). Overall, these Flx-regulated changes in synaptic and mitochondrial proteins of CSIS rats might be critical targets for new therapeutic development for the treatment of MDD. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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15 pages, 2315 KiB

Open AccessArticle

Protein Alterations in Cardiac Ischemia/Reperfusion Revealed by Spatial-Omics

by Stephanie T. P. Mezger, Alma M. A. Mingels, Matthieu Soulié, Carine J. Peutz-Kootstra, Otto Bekers, Paul Mulder, Ron M. A. Heeren and Berta Cillero-Pastor

Int. J. Mol. Sci. 2022, 23(22), 13847; https://doi.org/10.3390/ijms232213847 - 10 Nov 2022

Cited by 6 | Viewed by 2520

Abstract

Myocardial infarction is the most common cause of death worldwide. An understanding of the alterations in protein pathways is needed in order to develop strategies that minimize myocardial damage. To identify the protein signature of cardiac ischemia/reperfusion (I/R) injury in rats, we combined, [...] Read more.

Myocardial infarction is the most common cause of death worldwide. An understanding of the alterations in protein pathways is needed in order to develop strategies that minimize myocardial damage. To identify the protein signature of cardiac ischemia/reperfusion (I/R) injury in rats, we combined, for the first time, protein matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and label-free proteomics on the same tissue section placed on a conductive slide. Wistar rats were subjected to I/R surgery and sacrificed after 24 h. Protein MALDI-MSI data revealed ischemia specific regions, and distinct profiles for the infarct core and border. Firstly, the infarct core, compared to histologically unaffected tissue, showed a significant downregulation of cardiac biomarkers, while an upregulation was seen for coagulation and immune response proteins. Interestingly, within the infarct tissue, alterations in the cytoskeleton reorganization and inflammation were found. This work demonstrates that a single tissue section can be used for protein-based spatial-omics, combining MALDI-MSI and label-free proteomics. Our workflow offers a new methodology to investigate the mechanisms of cardiac I/R injury at the protein level for new strategies to minimize damage after MI. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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26 pages, 8218 KiB

Open AccessArticle

Dynamin-like Protein 1 (DNML1) as a Molecular Target for Antibody-Based Immunotherapy to Treat Glaucoma

by Henrik Tonner, Selina Hunn, Nadine Auler, Carsten Schmelter, Norbert Pfeiffer and Franz H. Grus

Int. J. Mol. Sci. 2022, 23(21), 13618; https://doi.org/10.3390/ijms232113618 - 7 Nov 2022

Cited by 7 | Viewed by 2485

Abstract

Slow and progressive loss of retinal ganglion cells (RGCs) is the main characteristic of glaucoma, the second leading cause of blindness worldwide. Previous studies have shown that impaired mitochondrial dynamics could facilitate retinal neurodegeneration. Mitochondrial dynamics are regulated directly (fission) or more indirectly [...] Read more.

Slow and progressive loss of retinal ganglion cells (RGCs) is the main characteristic of glaucoma, the second leading cause of blindness worldwide. Previous studies have shown that impaired mitochondrial dynamics could facilitate retinal neurodegeneration. Mitochondrial dynamics are regulated directly (fission) or more indirectly (fusion) by dynamin-like protein 1 (DNML1). Therefore, DNM1L might be a promising target for an antibody-based approach to treat glaucoma. The consequences of targeting endogenous DNM1L by antibodies in a glaucoma animal model have not been investigated yet. Here, we show that the intravitreal application of an anti-DNM1L antibody showed protective effects regarding the survival of RGCs and their axons in the retinal nerve fiber layer (RNFL). Antibody treatment also improved retinal functionality, as observed by electroretinography (Ganzfeld ERG). Western blot analysis revealed altered DNM1L phosphorylation and altered expression of proteins related to apoptosis suggesting a decreased apoptosis rate. Mass spectrometry analysis revealed 28 up-regulated and 21 down-regulated proteins (p < 0.05) in both experimental groups. Protein pathway analysis showed that many proteins interacted directly with the target protein DNM1L and could be classified into three main protein clusters: Vesicle traffic-associated (NSF, SNCA, ARF1), mitochondrion-associated (HSP9A, SLC25A5/ANT2, GLUD1) and cytoskeleton-associated (MAP1A) signaling pathway. Our results demonstrate that DNM1L is a promising target for an antibody-based approach to glaucoma therapy. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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11 pages, 299 KiB

Open AccessCommunication

The Search for Associations of Serum Proteins with the Presence of Unstable Atherosclerotic Plaque in Coronary Atherosclerosis

by Ekaterina Mikhailovna Stakhneva, Elena Vladimirovna Kashtanova, Yana Vladimirovna Polonskaya, Eugeniia Vitalievna Striukova, Viktoriya Sergeevna Shramko, Evgeny Viktorovich Sadovski, Alexey Vitalievich Kurguzov, Ivan Sergeevich Murashov, Alexander Mikhailovich Chernyavskii and Yuliya Igorevna Ragino

Int. J. Mol. Sci. 2022, 23(21), 12795; https://doi.org/10.3390/ijms232112795 - 24 Oct 2022

Cited by 6 | Viewed by 1657

Abstract

To study the associations of blood proteins with the presence of unstable atherosclerotic plaques in the arteries of patients with coronary atherosclerosis using quantitative proteomics. The studies involved two groups of men with coronary atherosclerosis (group 1 (St) had only stable atherosclerotic plaques; [...] Read more.

To study the associations of blood proteins with the presence of unstable atherosclerotic plaques in the arteries of patients with coronary atherosclerosis using quantitative proteomics. The studies involved two groups of men with coronary atherosclerosis (group 1 (St) had only stable atherosclerotic plaques; group 2 (Ns) had only unstable atherosclerotic plaques, according to histological analysis of tissue samples); the average age of patients was 57.95 ± 7.22. Protein concentrations in serum samples were determined using the PeptiQuant Plus Proteomics Kit. The identification of protein fractions was carried out by monitoring multiple reactions on a Q-TRAP 6500 mass spectrometer combined with a liquid chromatograph. Mass spectrometric identification revealed in serum samples from patients with unstable atherosclerotic plaques a reduced concentration of proteins in the blood: α-1-acid glycoprotein, α-1-antichymotrypsin, α-1-antitrypsin, ceruloplasmin, hemopexin, haptoglobin, apolipoprotein B-100, apolipoprotein L1, afamin and complement component (C3, C7, C9). Moreover, at the same time a high concentration complements factor H and attractin. The differences were considered significant at p < 0.05. It was found that the instability of atherosclerotic plaques is associated with the concentration of proteins: afamin, attractin, components of the complement system, hemopexin and haptoglobin. The data of our study showed the association of some blood proteins with the instability of atherosclerotic plaques in coronary atherosclerosis. Their potential role in the development of this disease and the possibility of using the studied proteins as biomarkers requires further research. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

22 pages, 3803 KiB

Open AccessArticle

Proteomics Profiling of Stool Samples from Preterm Neonates with SWATH/DIA Mass Spectrometry for Predicting Necrotizing Enterocolitis

by David Gagné, Elmira Shajari, Marie-Pier Thibault, Jean-François Noël, François-Michel Boisvert, Corentin Babakissa, Emile Levy, Hugo Gagnon, Marie A. Brunet, David Grynspan, Emanuela Ferretti, Valérie Bertelle and Jean-François Beaulieu

Int. J. Mol. Sci. 2022, 23(19), 11601; https://doi.org/10.3390/ijms231911601 - 1 Oct 2022

Cited by 4 | Viewed by 2691

Abstract

Necrotizing enterocolitis (NEC) is a life-threatening condition for premature infants in neonatal intensive care units. Finding indicators that can predict NEC development before symptoms appear would provide more time to apply targeted interventions. In this study, stools from 132 very-low-birth-weight (VLBW) infants were [...] Read more.

Necrotizing enterocolitis (NEC) is a life-threatening condition for premature infants in neonatal intensive care units. Finding indicators that can predict NEC development before symptoms appear would provide more time to apply targeted interventions. In this study, stools from 132 very-low-birth-weight (VLBW) infants were collected daily in the context of a multi-center prospective study aimed at investigating the potential of fecal biomarkers for NEC prediction using proteomics technology. Eight of the VLBW infants received a stage-3 NEC diagnosis. Stools collected from the NEC infants up to 10 days before their diagnosis were available for seven of them. Their samples were matched with those from seven pairs of non-NEC controls. The samples were processed for liquid chromatography-tandem mass spectrometry analysis using SWATH/DIA acquisition and cross-compatible proteomic software to perform label-free quantification. ROC curve and principal component analyses were used to explore discriminating information and to evaluate candidate protein markers. A series of 36 proteins showed the most efficient capacity with a signature that predicted all seven NEC infants at least a week in advance. Overall, our study demonstrates that multiplexed proteomic signature detection constitutes a promising approach for the early detection of NEC development in premature infants. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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19 pages, 3611 KiB

Open AccessArticle

Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure

by Hoi-lam Li, Sze Wan Shan, W. Daniel Stamer, King-kit Li, Henry Ho-lung Chan, Mortimer M. Civan, Chi-ho To, Thomas Chuen Lam and Chi-wai Do

Int. J. Mol. Sci. 2022, 23(13), 7372; https://doi.org/10.3390/ijms23137372 - 1 Jul 2022

Cited by 4 | Viewed by 2762

Abstract

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and [...] Read more.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and has been shown to regulate cell contraction, fluid secretion, and ECM remodeling in various cell types, suggesting the potential significance of regulating outflow resistance and IOP. We demonstrated that Ba significantly lowered the IOP by about 5 mmHg in living mice. Consistent with that, Ba increased the outflow facility by up to 90% in enucleated mouse eyes. The effects of Ba on cell volume regulation and contractility were examined in primary human TM (hTM) cells. We found that Ba (1–100 µM) had no effect on cell volume under iso-osmotic conditions but inhibited the regulatory volume decrease (RVD) by up to 70% under hypotonic challenge. In addition, Ba relaxed hTM cells via reduced myosin light chain (MLC) phosphorylation. Using iTRAQ-based quantitative proteomics, 47 proteins were significantly regulated in hTM cells after a 3-h Ba treatment. Ba significantly increased the expression of cathepsin B by 1.51-fold and downregulated the expression of D-dopachrome decarboxylase and pre-B-cell leukemia transcription factor-interacting protein 1 with a fold-change of 0.58 and 0.40, respectively. We suggest that a Ba-mediated increase in outflow facility is triggered by cell relaxation via MLC phosphorylation along with inhibiting RVD in hTM cells. The Ba-mediated changes in protein expression support the notion of altered ECM homeostasis, potentially contributing to a reduction of outflow resistance and thereby IOP. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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22 pages, 4488 KiB

Open AccessArticle

Heat Shock Alters the Proteomic Profile of Equine Mesenchymal Stem Cells

by Ahmad Abd-El-Aziz, Angela Riveroll, Blanca Esparza-Gonsalez, Laurie McDuffee, Alejandro M. Cohen, Adam L. Fenech and William J. Montelpare

Int. J. Mol. Sci. 2022, 23(13), 7233; https://doi.org/10.3390/ijms23137233 - 29 Jun 2022

Cited by 2 | Viewed by 2042

Abstract

The aim of this research was to determine the impact of heat stress on cell differentiation in an equine mesenchymal stem cell model (EMSC) through the application of heat stress to primary EMSCs as they progressed through the cell specialization process. A proteomic [...] Read more.

The aim of this research was to determine the impact of heat stress on cell differentiation in an equine mesenchymal stem cell model (EMSC) through the application of heat stress to primary EMSCs as they progressed through the cell specialization process. A proteomic analysis was performed using mass spectrometry to compare relative protein abundances among the proteomes of three cell types: progenitor EMSCs and differentiated osteoblasts and adipocytes, maintained at 37 °C and 42 °C during the process of cell differentiation. A cell-type and temperature-specific response to heat stress was observed, and many of the specific differentially expressed proteins were involved in cell-signaling pathways such as Notch and Wnt signaling, which are known to regulate cellular development. Furthermore, cytoskeletal proteins profilin, DSTN, SPECC1, and DAAM2 showed increased protein levels in osteoblasts differentiated at 42 °C as compared with 37 °C, and these cells, while they appeared to accumulate calcium, did not organize into a whorl agglomerate as is typically seen at physiological temperatures. This altered proteome composition observed suggests that heat stress could have long-term impacts on cellular development. We propose that this in vitro stem cell culture model of cell differentiation is useful for investigating molecular mechanisms that impact cell development in response to stressors. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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20 pages, 3526 KiB

Open AccessArticle

Characterization of the Secretome of a Specific Cell Expressing Mutant Methionyl-tRNA Synthetase in Co-Culture Using Click Chemistry

by Sungho Shin, Seonjeong Lee, Sunyoung Choi, Narae Park, Yumi Kwon, Jaehoon Jeong, Shinyeong Ju, Yunsil Chang, Kangsik Park, Chulwon Ha and Cheolju Lee

Int. J. Mol. Sci. 2022, 23(12), 6527; https://doi.org/10.3390/ijms23126527 - 10 Jun 2022

Cited by 5 | Viewed by 2925

Abstract

Co-culture system, in which two or more distinct cell types are cultured together, is advantageous in that it can mimic the environment of the in vivo niche of the cells. In this study, we presented a strategy to analyze the secretome of a [...] Read more.

Co-culture system, in which two or more distinct cell types are cultured together, is advantageous in that it can mimic the environment of the in vivo niche of the cells. In this study, we presented a strategy to analyze the secretome of a specific cell type under the co-culture condition in serum-supplemented media. For the cell-specific secretome analysis, we expressed the mouse mutant methionyl-tRNA synthetase for the incorporation of the non-canonical amino acid, azidonorleucine into the newly synthesized proteins in cells of which the secretome is targeted. The azidonorleucine-tagged secretome could be enriched, based on click chemistry, and distinguished from any other contaminating proteins, either from the cell culture media or the other cells co-cultured with the cells of interest. In order to have more reliable true-positive identifications of cell-specific secretory bodies, we established criteria to exclude any identified human peptide matched to bovine proteins. As a result, we identified a maximum of 719 secreted proteins in the secretome analysis under this co-culture condition. Last, we applied this platform to profile the secretome of mesenchymal stem cells and predicted its therapeutic potential on osteoarthritis based on secretome analysis. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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17 pages, 5501 KiB

Open AccessArticle

Retinal Proteomic Analysis in a Mouse Model of Endotoxin-Induced Uveitis Using Data-Independent Acquisition-Based Mass Spectrometry

by Jing Zhang, Jiangmei Wu, Daqian Lu, Chi-Ho To, Thomas Chuen Lam and Bin Lin

Int. J. Mol. Sci. 2022, 23(12), 6464; https://doi.org/10.3390/ijms23126464 - 9 Jun 2022

Cited by 4 | Viewed by 2990

Abstract

Uveitis is a group of sight-threatening ocular inflammatory diseases, potentially leading to permanent vision loss in patients. However, it remains largely unknown how uveitis causes retinal malfunction and vision loss. Endotoxin-induced uveitis (EIU) in rodents is a good animal model to study uveitis [...] Read more.

Uveitis is a group of sight-threatening ocular inflammatory diseases, potentially leading to permanent vision loss in patients. However, it remains largely unknown how uveitis causes retinal malfunction and vision loss. Endotoxin-induced uveitis (EIU) in rodents is a good animal model to study uveitis and associated acute retinal inflammation. To understand the pathogenic mechanism of uveitis and screen potential targets for treatment, we analyzed the retinal proteomic profile of the EIU mouse model using a data-independent acquisition-based mass spectrometry (SWATH-MS). After systemic LPS administration, we observed activation of microglial cells accompanied with the elevation of pro-inflammatory mediators and visual function declines. In total, we observed 79 upregulated and 90 downregulated differentially expressed proteins (DEPs). Among the DEPs, we found that histone family members (histone H1, H2A, H2B) and blood proteins including haptoglobin (HP), hemopexin (HPX), and fibrinogen gamma chain (FGG) were dramatically increased in EIU groups relative to those in control groups. We identified phototransduction and synaptic vesicle cycle as the top two significant KEGG pathways. Moreover, canonical pathway analysis on DEPs using Ingenuity Pathway Analysis revealed top three most significant enriched pathways related to acute phase response signaling, synaptogenesis signaling, and eif2 signaling. We further confirmed upregulation of several DEPs associated with the acute phase response signaling including HP, HPX, and FGG in LPS-treated retinas by qPCR and Western blot. In summary, this study serves as the first report to detect retinal proteome changes in the EIU model. The study provides several potential candidates for exploring the mechanism and novel therapeutic targets for uveitis and other retinal inflammatory diseases. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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29 pages, 4377 KiB

Open AccessArticle

Tandem Mass Tagging (TMT) Reveals Tissue-Specific Proteome of L4 Larvae of Anisakis simplex s. s.: Enzymes of Energy and/or Carbohydrate Metabolism as Potential Drug Targets in Anisakiasis

by Robert Stryiński, Jesús Mateos, Mónica Carrera, Jan Paweł Jastrzębski, Iwona Bogacka and Elżbieta Łopieńska-Biernat

Int. J. Mol. Sci. 2022, 23(8), 4336; https://doi.org/10.3390/ijms23084336 - 14 Apr 2022

Cited by 4 | Viewed by 3971

Abstract

Anisakis simplex s. s. is a parasitic nematode of marine mammals and causative agent of anisakiasis in humans. The cuticle and intestine of the larvae are the tissues most responsible for direct and indirect contact, respectively, of the parasite with the host. At [...] Read more.

Anisakis simplex s. s. is a parasitic nematode of marine mammals and causative agent of anisakiasis in humans. The cuticle and intestine of the larvae are the tissues most responsible for direct and indirect contact, respectively, of the parasite with the host. At the L4 larval stage, tissues, such as the cuticle and intestine, are fully developed and functional, in contrast to the L3 stage. As such, this work provides for the first time the tissue-specific proteome of A. simplex s. s. larvae in the L4 stage. Statistical analysis (FC ≥ 2; p-value ≤ 0.01) showed that 107 proteins were differentially regulated (DRPs) between the cuticle and the rest of the larval body. In the comparison between the intestine and the rest of the larval body at the L4 stage, 123 proteins were identified as DRPs. Comparison of the individual tissues examined revealed a total of 272 DRPs, with 133 proteins more abundant in the cuticle and 139 proteins more abundant in the intestine. Detailed functional analysis of the identified proteins was performed using bioinformatics tools. Glycolysis and the tricarboxylic acid cycle were the most enriched metabolic pathways by cuticular and intestinal proteins, respectively, in the L4 stage of A. simplex s. s. The presence of two proteins, folliculin (FLCN) and oxoglutarate dehydrogenase (OGDH), was confirmed by Western blot, and their tertiary structure was predicted and compared with other species. In addition, host–pathogen interactions were identified, and potential new allergens were predicted. The result of this manuscript shows the largest number of protein identifications to our knowledge using proteomics tools for different tissues of L4 larvae of A. simplex s. s. The identified tissue-specific proteins could serve as targets for new drugs against anisakiasis. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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22 pages, 7182 KiB

Open AccessArticle

Proteomic Profiling of Saliva and Tears in Radiated Head and Neck Cancer Patients as Compared to Primary Sjögren’s Syndrome Patients

by Håvard Hynne, Lara A. Aqrawi, Janicke Liaaen Jensen, Bernd Thiede, Øyvind Palm, Cecilie Delphin Amdal, Kristine Løken Westgaard, Bente Brokstad Herlofson, Tor P. Utheim and Hilde Kanli Galtung

Int. J. Mol. Sci. 2022, 23(7), 3714; https://doi.org/10.3390/ijms23073714 - 28 Mar 2022

Cited by 11 | Viewed by 6051

Abstract

Patients with head and neck cancer (HNC) and patients with primary Sjögren’s syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve [...] Read more.

Patients with head and neck cancer (HNC) and patients with primary Sjögren’s syndrome (pSS) may exhibit similar symptoms of dry mouth and dry eyes, as a result of radiotherapy (RT) or a consequence of disease progression. To identify the proteins that may serve as promising disease biomarkers, we analysed saliva and tears from 29 radiated HNC patients and 21 healthy controls, and saliva from 14 pSS patients by mass spectrometry-based proteomics. The study revealed several upregulated, and in some instances overlapping, proteins in the two patient groups. Histone H1.4 and neutrophil collagenase were upregulated in whole saliva of both patient groups, while caspase-14, histone H4, and protein S100-A9 were upregulated in HNC saliva only. In HCN tear fluid, the most highly upregulated protein was mucin-like protein 1. These overexpressed proteins in saliva and tears play central roles in inflammation, host cell injury, activation of reactive oxygen species, and tissue repair. In conclusion, the similarities and differences in overexpressed proteins detected in saliva from HNC and pSS patients may contribute to the overall understanding of the different pathophysiological mechanisms inducing dry mouth. Thus, the recurring proteins identified could possibly serve as future promising biomarkers Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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Review

Jump to: Research

23 pages, 1814 KiB

Open AccessReview

Proteomics in Inherited Metabolic Disorders

by Maria del Pilar Chantada-Vázquez, Susana B. Bravo, Sofía Barbosa-Gouveia, José V. Alvarez and María L. Couce

Int. J. Mol. Sci. 2022, 23(23), 14744; https://doi.org/10.3390/ijms232314744 - 25 Nov 2022

Cited by 13 | Viewed by 3655

Abstract

Inherited metabolic disorders (IMD) are rare medical conditions caused by genetic defects that interfere with the body’s metabolism. The clinical phenotype is highly variable and can present at any age, although it more often manifests in childhood. The number of treatable IMDs has [...] Read more.

Inherited metabolic disorders (IMD) are rare medical conditions caused by genetic defects that interfere with the body’s metabolism. The clinical phenotype is highly variable and can present at any age, although it more often manifests in childhood. The number of treatable IMDs has increased in recent years, making early diagnosis and a better understanding of the natural history of the disease more important than ever. In this review, we discuss the main challenges faced in applying proteomics to the study of IMDs, and the key advances achieved in this field using tandem mass spectrometry (MS/MS). This technology enables the analysis of large numbers of proteins in different body fluids (serum, plasma, urine, saliva, tears) with a single analysis of each sample, and can even be applied to dried samples. MS/MS has thus emerged as the tool of choice for proteome characterization and has provided new insights into many diseases and biological systems. In the last 10 years, sequential window acquisition of all theoretical fragmentation spectra mass spectrometry (SWATH-MS) has emerged as an accurate, high-resolution technique for the identification and quantification of proteins differentially expressed between healthy controls and IMD patients. Proteomics is a particularly promising approach to help obtain more information on rare genetic diseases, including identification of biomarkers to aid early diagnosis and better understanding of the underlying pathophysiology to guide the development of new therapies. Here, we summarize new and emerging proteomic technologies and discuss current uses and limitations of this approach to identify and quantify proteins. Moreover, we describe the use of proteomics to identify the mechanisms regulating complex IMD phenotypes; an area of research essential to better understand these rare disorders and many other human diseases. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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21 pages, 1282 KiB

Open AccessReview

Biomarkers in Neurodegenerative Diseases: Proteomics Spotlight on ALS and Parkinson’s Disease

by Rekha Raghunathan, Kathleen Turajane and Li Chin Wong

Int. J. Mol. Sci. 2022, 23(16), 9299; https://doi.org/10.3390/ijms23169299 - 18 Aug 2022

Cited by 24 | Viewed by 6496

Abstract

Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons and the loss of behavioral functions. Both diseases lack biomarkers for diagnosis and treatment efficacy. Proteomics [...] Read more.

Neurodegenerative diseases such as amyotrophic lateral sclerosis (ALS) and Parkinson’s disease (PD) are both characterized by pathogenic protein aggregates that correlate with the progressive degeneration of neurons and the loss of behavioral functions. Both diseases lack biomarkers for diagnosis and treatment efficacy. Proteomics is an unbiased quantitative tool capable of the high throughput quantitation of thousands of proteins from minimal sample volumes. We review recent proteomic studies in human tissues, plasma, cerebrospinal fluid (CSF), and exosomes in ALS and PD that identify proteins with potential utility as biomarkers. Further, we review disease-related post-translational modifications in key proteins TDP43 in ALS and α-synuclein in PD studies, which may serve as biomarkers. We compare relative and absolute quantitative proteomic approaches in key biomarker studies in ALS and PD and discuss recent technological advancements which may identify suitable biomarkers for the early-diagnosis treatment efficacy of these diseases. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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16 pages, 781 KiB

Open AccessReview

Clinical Tear Fluid Proteomics—A Novel Tool in Glaucoma Research

by Janika Nättinen, Ulla Aapola, Praveena Nukareddy and Hannu Uusitalo

Int. J. Mol. Sci. 2022, 23(15), 8136; https://doi.org/10.3390/ijms23158136 - 23 Jul 2022

Cited by 8 | Viewed by 4055

Abstract

Tear fluid forms the outermost layer of the ocular surface and its characteristics and composition have been connected to various ocular surface diseases. As tear proteomics enables the non-invasive investigation of protein levels in the tear fluid, it has become an increasingly popular [...] Read more.

Tear fluid forms the outermost layer of the ocular surface and its characteristics and composition have been connected to various ocular surface diseases. As tear proteomics enables the non-invasive investigation of protein levels in the tear fluid, it has become an increasingly popular approach in ocular surface and systemic disease studies. Glaucoma, which is a set of multifactorial diseases affecting mainly the optic nerve and retinal ganglion cells, has also been studied using tear proteomics. In this condition, the complete set of pathophysiological changes occurring in the eye is not yet fully understood, and biomarkers for early diagnosis and accurate treatment selection are needed. More in-depth analyses of glaucoma tear proteomics have started to emerge only more recently with the implementation of LC-MS/MS and other modern technologies. The aim of this review was to examine the published data of the tear protein changes occurring during glaucoma, its topical treatment, and surgical interventions. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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13 pages, 3577 KiB

Open AccessReview

Chemical Probes and Activity-Based Protein Profiling for Cancer Research

by Mohammad Faysal Al Mazid, Seung Bin Park, Subba Rao Cheekatla, Dhiraj P. Murale, Kyung Ho Shin and Jun-Seok Lee

Int. J. Mol. Sci. 2022, 23(11), 5936; https://doi.org/10.3390/ijms23115936 - 25 May 2022

Cited by 5 | Viewed by 3560

Abstract

Chemical probes can be used to understand the complex biological nature of diseases. Due to the diversity of cancer types and dynamic regulatory pathways involved in the disease, there is a need to identify signaling pathways and associated proteins or enzymes that are [...] Read more.

Chemical probes can be used to understand the complex biological nature of diseases. Due to the diversity of cancer types and dynamic regulatory pathways involved in the disease, there is a need to identify signaling pathways and associated proteins or enzymes that are traceable or detectable in tests for cancer diagnosis and treatment. Currently, fluorogenic chemical probes are widely used to detect cancer-associated proteins and their binding partners. These probes are also applicable in photodynamic therapy to determine drug efficacy and monitor regulating factors. In this review, we discuss the synthesis of chemical probes for different cancer types from 2016 to the present time and their application in monitoring the activity of transferases, hydrolases, deacetylases, oxidoreductases, and immune cells. Moreover, we elaborate on their potential roles in photodynamic therapy. Full article

(This article belongs to the Special Issue Proteomics and Its Applications in Disease)

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