Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
7.8
5.6
Journals
IJMS
Special Issues
Metalloproteins 2017
ijms-logo
Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

► Journal Menu

Journal Browser

► Journal Browser
share announcement

Metalloproteins 2017

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (28 February 2017) | Viewed by 120949

Special Issue Editor

Prof. Dr. Masatoshi Maki

E-Mail Website
Guest Editor
Graduate School of Bioagricultural Sciences, Nagoya University, Nagoya 464-8601, Japan
Interests: calcium-binding protein; calcium signaling; protein-protein interaction; post-transcriptional regulation; protein structure; membrane traffic
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

A variety of abundant and trace metals are taken up into cells and used for biological processes. Metals are incorporated into proteins in the form of simple ions or clusters, or with cofactors. Metalloproteins play important roles in living organisms by functioning as enzymatic catalysts, regulators, photosynthetic and respiration electron-transfer chain, metal ion transporters, signaling sensors, transcription factors, etc. Understanding of metalloproteins in animals, plants, protists, and microorganisms should expand, not only our knowledge of life on Earth, but also the origin of life and extraterrestrial life, if any exists. Detoxification of heavy metals is also of great concern in environmental pollution.

This Special Issue of Metalloproteins welcomes contributions in all areas of basic and application-oriented research associated with metalloproteins from the aspects of biochemistry, molecular biology, and biophysics.

Prof. Dr. Masatoshi Maki
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Alkaline and alkaline-earth metals
  • Artificial metalloproteins
  • Binding motif
  • Buffering action
  • Cell signaling
  • Cofactor
  • Coordination
  • Dietary minerals
  • Enzyme catalysis
  • Heavy metal stress
  • Metal affinity chromatography
  • Metal-ion transporters
  • Protein engineering
  • Protein-protein interaction
  • Sensor protein
  • Trace elements
  • Transcription factors
  • Transition metals

Related Special Issue

Published Papers (17 papers)

Download All Papers
Order results
Result details
Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:

Research

Jump to: Review

2216 KiB  
Article
The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice
by Lakshini Herat, Caroline Rudnicka, Yasunori Okada, Satsuki Mochizuki, Markus Schlaich and Vance Matthews
Int. J. Mol. Sci. 2017, 18(4), 884; https://doi.org/10.3390/ijms18040884 - 21 Apr 2017
Cited by 9 | Viewed by 4372
Abstract
Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. [...] Read more.
Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity. We identified that ADAM28 mRNA and protein expression was markedly increased in the livers of mice with the metabolic syndrome. In addition, noradrenaline, the major neurotransmitter of the sympathetic nervous system, results in elevated Adam28 mRNA expression in human monocytes. Downregulation of ADAM28 with siRNA technology resulted in a lack of weight gain, promotion of insulin sensitivity/glucose tolerance and decreased liver tumour necrosis factor-α (TNF-α) levels in our diet-induced obesity mouse model as well as reduced blood urea nitrogen, alkaline phosphatase and aspartate aminotransferase. In addition, we show that ADAM28 knock-out mice also displayed reduced body weight, elevated high density lipoprotein cholesterol levels, and reductions in blood urea nitrogen, alkaline phosphatase, and aspartate aminotransferase. The results of this study provide important insights into the pathogenic role of the metalloproteinase ADAM28 in the metabolic syndrome and suggests that downregulation of ADAM28 may be a potential therapeutic strategy in the metabolic syndrome. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Figure 1

8516 KiB  
Article
Metallothionein Gene Family in the Sea Urchin Paracentrotus lividus: Gene Structure, Differential Expression and Phylogenetic Analysis
by Maria Antonietta Ragusa, Aldo Nicosia, Salvatore Costa, Angela Cuttitta and Fabrizio Gianguzza
Int. J. Mol. Sci. 2017, 18(4), 812; https://doi.org/10.3390/ijms18040812 - 12 Apr 2017
Cited by 23 | Viewed by 6431
Abstract
Metallothioneins (MT) are small and cysteine-rich proteins that bind metal ions such as zinc, copper, cadmium, and nickel. In order to shed some light on MT gene structure and evolution, we cloned seven Paracentrotus lividus MT genes, comparing them to Echinodermata and Chordata [...] Read more.
Metallothioneins (MT) are small and cysteine-rich proteins that bind metal ions such as zinc, copper, cadmium, and nickel. In order to shed some light on MT gene structure and evolution, we cloned seven Paracentrotus lividus MT genes, comparing them to Echinodermata and Chordata genes. Moreover, we performed a phylogenetic analysis of 32 MTs from different classes of echinoderms and 13 MTs from the most ancient chordates, highlighting the relationships between them. Since MTs have multiple roles in the cells, we performed RT-qPCR and in situ hybridization experiments to understand better MT functions in sea urchin embryos. Results showed that the expression of MTs is regulated throughout development in a cell type-specific manner and in response to various metals. The MT7 transcript is expressed in all tissues, especially in the stomach and in the intestine of the larva, but it is less metal-responsive. In contrast, MT8 is ectodermic and rises only at relatively high metal doses. MT5 and MT6 expression is highly stimulated by metals in the mesenchyme cells. Our results suggest that the P. lividus MT family originated after the speciation events by gene duplications, evolving developmental and environmental sub-functionalization. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

2517 KiB  
Article
Study of Different Variants of Mo Enzyme crARC and the Interaction with Its Partners crCytb5-R and crCytb5-1
by Alejandro Chamizo-Ampudia, Aurora Galvan, Emilio Fernandez and Angel Llamas
Int. J. Mol. Sci. 2017, 18(3), 670; https://doi.org/10.3390/ijms18030670 - 21 Mar 2017
Cited by 8 | Viewed by 3771
Abstract
The mARC (mitochondrial Amidoxime Reducing Component) proteins are recently discovered molybdenum (Mo) Cofactor containing enzymes. They are involved in the reduction of several N-hydroxylated compounds (NHC) and nitrite. Some NHC are prodrugs containing an amidoxime structure or mutagens such as 6-hydroxylaminopurine (HAP). [...] Read more.
The mARC (mitochondrial Amidoxime Reducing Component) proteins are recently discovered molybdenum (Mo) Cofactor containing enzymes. They are involved in the reduction of several N-hydroxylated compounds (NHC) and nitrite. Some NHC are prodrugs containing an amidoxime structure or mutagens such as 6-hydroxylaminopurine (HAP). We have studied this protein in the green alga Chlamydomonas reinhardtii (crARC). Interestingly, all the ARC proteins need the reducing power supplied by other proteins. It is known that crARC requires a cytochrome b5 (crCytb5-1) and a cytochrome b5 reductase (crCytb5-R) that form an electron transport chain from NADH to the substrates. Here, we have investigated NHC reduction by crARC, the interaction with its partners and the function of important conserved amino acids. Interactions among crARC, crCytb5-1 and crCytb5-R have been studied by size-exclusion chromatography. A protein complex between crARC, crCytb5-1 and crCytb5-R was identified. Twelve conserved crARC amino acids have been substituted by alanine by in vitro mutagenesis. We have determined that the amino acids D182, F210 and R276 are essential for NHC reduction activity, R276 is important and F210 is critical for the Mo Cofactor chelation. Finally, the crARC C-termini were shown to be involved in protein aggregation or oligomerization. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Figure 1

5674 KiB  
Article
Influence of Transgenic Metallothionein-1 on Gliosis, CA1 Neuronal Loss, and Brain Metal Levels of the Tg2576 Mouse Model of Alzheimer’s Disease
by Gemma Comes, Yasmina Manso, Anna Escrig, Olaya Fernandez-Gayol, Paula Sanchis, Amalia Molinero, Mercedes Giralt, Javier Carrasco and Juan Hidalgo
Int. J. Mol. Sci. 2017, 18(2), 251; https://doi.org/10.3390/ijms18020251 - 26 Jan 2017
Cited by 8 | Viewed by 5245
Abstract
The mouse model of Alzheimer’s disease (AD), Tg2576 mice (APP), has provided valuable information, such as the role of the metallothionein (MT) family in their behavioral and amyloidosis phenotypes. In this study, we further characterize the role of MT-1 by crossing Mt1-overexpressing [...] Read more.
The mouse model of Alzheimer’s disease (AD), Tg2576 mice (APP), has provided valuable information, such as the role of the metallothionein (MT) family in their behavioral and amyloidosis phenotypes. In this study, we further characterize the role of MT-1 by crossing Mt1-overexpressing mice with Tg2576 mice (APPTgMT). In 14-month-old mice, MT-1(/2) protein levels were dramatically increased by Mt1 overexpression throughout the cortex (Cx), which showed a prominent caudal-rostral gradient, and the hippocampus (HC). There was a trend for MT-1(/2) immunostaining to be increased in the areas surrounding the amyloid plaques in control male mice but not in Mt1-overexpressing mice. Gliosis was elicited by the amyloid plaques, but the effects of Mt1 overexpression were modest. However, in hippocampal western blots the microglial marker Iba-1 was increased in old male APPTgMT mice compared to APP-wild type (APPWT) mice, and the opposite was observed in young mice. Hippocampal CA1 neuronal loss was observed in Tg2576 mice, but was unaffected by Mt1 overexpression. Aging increased Zn and Cu levels differently depending on brain area, sex, and genotype. Thus, the effects of Mt1 overexpression on the phenotype of Tg2576 mice here studied are modest. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

6538 KiB  
Article
MMP-3 Deficiency Alleviates Endotoxin-Induced Acute Inflammation in the Posterior Eye Segment
by Inge Van Hove, Evy Lefevere, Lies De Groef, Jurgen Sergeys, Manuel Salinas-Navarro, Claude Libert, Roosmarijn Vandenbroucke and Lieve Moons
Int. J. Mol. Sci. 2016, 17(11), 1825; https://doi.org/10.3390/ijms17111825 - 01 Nov 2016
Cited by 24 | Viewed by 7413
Abstract
Matrix metalloproteinase-3 (MMP-3) is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE) and the [...] Read more.
Matrix metalloproteinase-3 (MMP-3) is known to mediate neuroinflammatory processes by activating microglia, disrupting blood–central nervous system barriers and supporting neutrophil influx into the brain. In addition, the posterior part of the eye, more specifically the retina, the retinal pigment epithelium (RPE) and the blood–retinal barrier, is affected upon neuroinflammation, but a role for MMP-3 during ocular inflammation remains elusive. We investigated whether MMP-3 contributes to acute inflammation in the eye using the endotoxin-induced uveitis (EIU) model. Systemic administration of lipopolysaccharide induced an increase in MMP-3 mRNA and protein expression level in the posterior part of the eye. MMP-3 deficiency or knockdown suppressed retinal leukocyte adhesion and leukocyte infiltration into the vitreous cavity in mice subjected to EIU. Moreover, retinal and RPE mRNA levels of intercellular adhesion molecule 1 (Icam1), interleukin 6 (Il6), cytokine-inducible nitrogen oxide synthase (Nos2) and tumor necrosis factor α (Tnfα), which are key molecules involved in EIU, were clearly reduced in MMP-3 deficient mice. In addition, loss of MMP-3 repressed the upregulation of the chemokines monocyte chemoattractant protein (MCP)-1 and (C-X-C motif) ligand 1 (CXCL1). These findings suggest a contribution of MMP-3 during EIU, and its potential use as a therapeutic drug target in reducing ocular inflammation. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

12369 KiB  
Article
Experimental Dissection of Metalloproteinase Inhibition-Mediated and Toxic Effects of Phenanthroline on Zebrafish Development
by Tonya R. Ellis and Bryan D. Crawford
Int. J. Mol. Sci. 2016, 17(9), 1503; https://doi.org/10.3390/ijms17091503 - 08 Sep 2016
Cited by 10 | Viewed by 6648
Abstract
Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodeling, cell-signaling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN) is an inexpensive, broad-spectrum inhibitor of [...] Read more.
Metalloproteinases are zinc-dependent endopeptidases that function as primary effectors of tissue remodeling, cell-signaling, and many other roles. Their regulation is ferociously complex, and is exquisitely sensitive to their molecular milieu, making in vivo studies challenging. Phenanthroline (PhN) is an inexpensive, broad-spectrum inhibitor of metalloproteinases that functions by chelating the catalytic zinc ion, however its use in vivo has been limited due to suspected off-target effects. PhN is very similar in structure to phenanthrene (PhE), a well-studied poly aromatic hydrocarbon (PAH) known to cause toxicity in aquatic animals by activating the aryl hydrocarbon receptor (AhR). We show that zebrafish are more sensitive to PhN than PhE, and that PhN causes a superset of the effects caused by PhE. Morpholino knock-down of the AhR rescues the effects of PhN that are shared with PhE, suggesting these are due to PAH toxicity. The effects of PhN that are not shared with PhE (specifically disruption of neural crest development and angiogenesis) involve processes known to depend on metalloproteinase activity. Furthermore these PhN-specific effects are not rescued by AhR knock-down, suggesting that these are bona fide effects of metalloproteinase inhibition, and that PhN can be used as a broad spectrum metalloproteinase inhibitor for studies with zebrafish in vivo. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

3585 KiB  
Article
Transcriptional Induction of Metallothionein by Tris(pentafluorophenyl)stibane in Cultured Bovine Aortic Endothelial Cells
by Tomoya Fujie, Masaki Murakami, Eiko Yoshida, Shuji Yasuike, Tomoki Kimura, Yasuyuki Fujiwara, Chika Yamamoto and Toshiyuki Kaji
Int. J. Mol. Sci. 2016, 17(9), 1381; https://doi.org/10.3390/ijms17091381 - 23 Aug 2016
Cited by 20 | Viewed by 5945
Abstract
Vascular endothelial cells cover the luminal surface of blood vessels and contribute to the prevention of vascular disorders such as atherosclerosis. Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, inducible protein, which protects cells from the toxicity of heavy metals and active [...] Read more.
Vascular endothelial cells cover the luminal surface of blood vessels and contribute to the prevention of vascular disorders such as atherosclerosis. Metallothionein (MT) is a low molecular weight, cysteine-rich, metal-binding, inducible protein, which protects cells from the toxicity of heavy metals and active oxygen species. Endothelial MT is not induced by inorganic zinc. Adequate tools are required to investigate the mechanisms underlying endothelial MT induction. In the present study, we found that an organoantimony compound, tris(pentafluorophenyl)stibane, induces gene expression of MT-1A and MT-2A, which are subisoforms of MT in bovine aortic endothelial cells. The data reveal that MT-1A is induced by activation of both the MTF-1–MRE and Nrf2–ARE pathways, whereas MT-2A expression requires only activation of the MTF-1–MRE pathway. The present data suggest that the original role of MT-1 is to protect cells from heavy metal toxicity and oxidative stress in the biological defense system, while that of MT-2 is to regulate intracellular zinc metabolism. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

Review

Jump to: Research

613 KiB  
Review
New Insights into the Role of Matrix Metalloproteinases in Preeclampsia
by Salvador Espino Y. Sosa, Arturo Flores-Pliego, Aurora Espejel-Nuñez, Diana Medina-Bastidas, Felipe Vadillo-Ortega, Veronica Zaga-Clavellina and Guadalupe Estrada-Gutierrez
Int. J. Mol. Sci. 2017, 18(7), 1448; https://doi.org/10.3390/ijms18071448 - 20 Jul 2017
Cited by 102 | Viewed by 9069
Abstract
Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs) exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A [...] Read more.
Preeclampsia is a severe pregnancy complication globally, characterized by poor placentation triggering vascular dysfunction. Matrix metalloproteinases (MMPs) exhibit proteolytic activity implicated in the efficiency of trophoblast invasion to the uterine wall, and a dysregulation of these enzymes has been linked to preeclampsia. A decrease in MMP-2 and MMP-9 interferes with the normal remodeling of spiral arteries at early pregnancy stages, leading to the initial pathophysiological changes observed in preeclampsia. Later in pregnancy, an elevation in MMP-2 and MMP-9 induces abnormal release of vasoactive factors conditioning hypertension. Although these two enzymes lead the scene, other MMPs like MMP-1 and MMP-14 seem to have a role in this pathology. This review gathers published recent evidence about the implications of different MMPs in preeclampsia, and the potential use of these enzymes as emergent biomarkers and biological therapeutic targets, focusing on studies involving human subjects. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Figure 1

1093 KiB  
Review
The Role of Hemoproteins: Hemoglobin, Myoglobin and Neuroglobin in Endogenous Thiosulfate Production Processes
by Anna Bilska-Wilkosz, Małgorzata Iciek, Magdalena Górny and Danuta Kowalczyk-Pachel
Int. J. Mol. Sci. 2017, 18(6), 1315; https://doi.org/10.3390/ijms18061315 - 20 Jun 2017
Cited by 22 | Viewed by 7454
Abstract
Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to sulfate while hydrogen sulfide is transformed into thiosulfate. These processes occurring mostly in mitochondria are described as a canonical hydrogen sulfide [...] Read more.
Thiosulfate formation and biodegradation processes link aerobic and anaerobic metabolism of cysteine. In these reactions, sulfite formed from thiosulfate is oxidized to sulfate while hydrogen sulfide is transformed into thiosulfate. These processes occurring mostly in mitochondria are described as a canonical hydrogen sulfide oxidation pathway. In this review, we discuss the current state of knowledge on the interactions between hydrogen sulfide and hemoglobin, myoglobin and neuroglobin and postulate that thiosulfate is a metabolically important product of this processes. Hydrogen sulfide oxidation by ferric hemoglobin, myoglobin and neuroglobin has been defined as a non-canonical hydrogen sulfide oxidation pathway. Until recently, it appeared that the goal of thiosulfate production was to delay irreversible oxidation of hydrogen sulfide to sulfate excreted in urine; while thiosulfate itself was only an intermediate, transient metabolite on the hydrogen sulfide oxidation pathway. In the light of data presented in this paper, it seems that thiosulfate is a molecule that plays a prominent role in the human body. Thus, we hope that all these findings will encourage further studies on the role of hemoproteins in the formation of this undoubtedly fascinating molecule and on the mechanisms responsible for its biological activity in the human body. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

1515 KiB  
Review
Matrix Metalloproteinase Gene Activation Resulting from Disordred Epigenetic Mechanisms in Rheumatoid Arthritis
by Yasuto Araki and Toshihide Mimura
Int. J. Mol. Sci. 2017, 18(5), 905; https://doi.org/10.3390/ijms18050905 - 25 Apr 2017
Cited by 84 | Viewed by 8619
Abstract
Matrix metalloproteinases (MMPs) are implicated in the degradation of extracellular matrix (ECM). Rheumatoid arthritis (RA) synovial fibroblasts (SFs) produce matrix-degrading enzymes, including MMPs, which facilitate cartilage destruction in the affected joints in RA. Epigenetic mechanisms contribute to change in the chromatin state, resulting [...] Read more.
Matrix metalloproteinases (MMPs) are implicated in the degradation of extracellular matrix (ECM). Rheumatoid arthritis (RA) synovial fibroblasts (SFs) produce matrix-degrading enzymes, including MMPs, which facilitate cartilage destruction in the affected joints in RA. Epigenetic mechanisms contribute to change in the chromatin state, resulting in an alteration of gene transcription. Recently, MMP gene activation has been shown to be caused in RASFs by the dysregulation of epigenetic changes, such as histone modifications, DNA methylation, and microRNA (miRNA) signaling. In this paper, we review the role of MMPs in the pathogenesis of RA as well as the disordered epigenetic mechanisms regulating MMP gene activation in RASFs. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Figure 1

729 KiB  
Review
Spondyloarthritis: Matrix Metalloproteinasesas Biomarkers of Pathogenesis and Response to Tumor Necrosis Factor (TNF) Inhibitors
by Stefania Moz, Ada Aita, Daniela Basso, Roberta Ramonda, Mario Plebani and Leonardo Punzi
Int. J. Mol. Sci. 2017, 18(4), 830; https://doi.org/10.3390/ijms18040830 - 14 Apr 2017
Cited by 17 | Viewed by 4628
Abstract
The term spondyloarthritis (SpA) is used to describe a group of multifactorial chronic inflammatory diseases characterized by a predisposing genetic background and clinical manifestations typically involving the sacroiliac joint. The absence of pathognomonic clinical and/or laboratory findings generally results in a delay in [...] Read more.
The term spondyloarthritis (SpA) is used to describe a group of multifactorial chronic inflammatory diseases characterized by a predisposing genetic background and clinical manifestations typically involving the sacroiliac joint. The absence of pathognomonic clinical and/or laboratory findings generally results in a delay in diagnosis and, consequently, in treatment. In addition, 20–40% of SpA patients are non-responders to tumor necrosis factor (TNF) inhibitor therapies. Given these considerations, it is important to identify biomarkers that can facilitate the diagnosis and assessment of disease activity. As inflammation plays a key role in the pathogenesis of SpA, inflammatory mediators have been investigated as potential biomarkers for diagnosing the disease and predicting response to therapy. Some investigators have focused their attention on the role of matrix metalloproteinases (MMPs), which are known to be markers of synovial inflammation that is generated in the joint in reaction to inflammatory stimuli. Several studies have been carried out to verify if serum MMPs levels could be useful to diagnose SpA, to assess disease severity, and to predict response to TNF inhibitor therapy. The current review focuses on MMPs’ role in SpA pathogenesis, diagnosis and therapeutic implications. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Figure 1

897 KiB  
Review
MMP-2 and 9 in Chronic Kidney Disease
by Zhengyuan Cheng, Manoj Hang Limbu, Zhi Wang, Jing Liu, Lei Liu, Xiaoyi Zhang, Pingsheng Chen and Bicheng Liu
Int. J. Mol. Sci. 2017, 18(4), 776; https://doi.org/10.3390/ijms18040776 - 08 Apr 2017
Cited by 101 | Viewed by 8533
Abstract
Gelatinases are members of the matrix metalloproteinase (MMPs) family; they play an important role in the degradation of the extracellular matrix (ECM). This effect is also crucial in the development and progression of chronic kidney disease (CKD). Its expression, as well as its [...] Read more.
Gelatinases are members of the matrix metalloproteinase (MMPs) family; they play an important role in the degradation of the extracellular matrix (ECM). This effect is also crucial in the development and progression of chronic kidney disease (CKD). Its expression, as well as its activity regulation are closely related to the cell signaling pathways, hypoxia and cell membrane structural change. Gelatinases also can affect the development and progression of CKD through the various interactions with tumor necrosis factors (TNFs), monocyte chemoattractant proteins (MCPs), growth factors (GFs), oxidative stress (OS), and so on. Currently, their non-proteolytic function is a hot topic of research, which may also be associated with the progression of CKD. Therefore, with the in-depth understanding about the function of gelatinases, we can have a more specific and accurate understanding of their role in the human body. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

5409 KiB  
Review
From Lipid Homeostasis to Differentiation: Old and New Functions of the Zinc Cluster Proteins Ecm22, Upc2, Sut1 and Sut2
by Ifeoluwapo Matthew Joshua and Thomas Höfken
Int. J. Mol. Sci. 2017, 18(4), 772; https://doi.org/10.3390/ijms18040772 - 05 Apr 2017
Cited by 25 | Viewed by 6211
Abstract
Zinc cluster proteins are a large family of transcriptional regulators with a wide range of biological functions. The zinc cluster proteins Ecm22, Upc2, Sut1 and Sut2 have initially been identified as regulators of sterol import in the budding yeast Saccharomyces cerevisiae. These [...] Read more.
Zinc cluster proteins are a large family of transcriptional regulators with a wide range of biological functions. The zinc cluster proteins Ecm22, Upc2, Sut1 and Sut2 have initially been identified as regulators of sterol import in the budding yeast Saccharomyces cerevisiae. These proteins also control adaptations to anaerobic growth, sterol biosynthesis as well as filamentation and mating. Orthologs of these zinc cluster proteins have been identified in several species of Candida. Upc2 plays a critical role in antifungal resistance in these important human fungal pathogens. Upc2 is therefore an interesting potential target for novel antifungals. In this review we discuss the functions, mode of actions and regulation of Ecm22, Upc2, Sut1 and Sut2 in budding yeast and Candida. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Figure 1

1124 KiB  
Review
Matrix Metalloproteinases as Regulators of Periodontal Inflammation
by Cavalla Franco, Hernández-Ríos Patricia, Sorsa Timo, Biguetti Claudia and Hernández Marcela
Int. J. Mol. Sci. 2017, 18(2), 440; https://doi.org/10.3390/ijms18020440 - 17 Feb 2017
Cited by 208 | Viewed by 10312
Abstract
Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of [...] Read more.
Periodontitis are infectious diseases characterized by immune-mediated destruction of periodontal supporting tissues and tooth loss. Matrix metalloproteinases (MMPs) are key proteases involved in destructive periodontal diseases. The study and interest in MMP has been fuelled by emerging evidence demonstrating the broad spectrum of molecules that can be cleaved by them and the myriad of biological processes that they can potentially regulate. The huge complexity of MMP functions within the ‘protease web’ is crucial for many physiologic and pathologic processes, including immunity, inflammation, bone resorption, and wound healing. Evidence points out that MMPs assemble in activation cascades and besides their classical extracellular matrix substrates, they cleave several signalling molecules—such as cytokines, chemokines, and growth factors, among others—regulating their biological functions and/or bioavailability during periodontal diseases. In this review, we provide an overview of emerging evidence of MMPs as regulators of periodontal inflammation. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

1808 KiB  
Review
The Function of the Mitochondrial Calcium Uniporter in Neurodegenerative Disorders
by Yajin Liao, Yuan Dong and Jinbo Cheng
Int. J. Mol. Sci. 2017, 18(2), 248; https://doi.org/10.3390/ijms18020248 - 10 Feb 2017
Cited by 48 | Viewed by 8069
Abstract
The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption [...] Read more.
The mitochondrial calcium uniporter (MCU)—a calcium uniporter on the inner membrane of mitochondria—controls the mitochondrial calcium uptake in normal and abnormal situations. Mitochondrial calcium is essential for the production of adenosine triphosphate (ATP); however, excessive calcium will induce mitochondrial dysfunction. Calcium homeostasis disruption and mitochondrial dysfunction is observed in many neurodegenerative disorders. However, the role and regulatory mechanism of the MCU in the development of these diseases are obscure. In this review, we summarize the role of the MCU in controlling oxidative stress-elevated mitochondrial calcium and its function in neurodegenerative disorders. Inhibition of the MCU signaling pathway might be a new target for the treatment of neurodegenerative disorders. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

3108 KiB  
Review
Structure-Functional Basis of Ion Transport in Sodium–Calcium Exchanger (NCX) Proteins
by Moshe Giladi, Reut Shor, Michal Lisnyansky and Daniel Khananshvili
Int. J. Mol. Sci. 2016, 17(11), 1949; https://doi.org/10.3390/ijms17111949 - 22 Nov 2016
Cited by 37 | Viewed by 7945
Abstract
The membrane-bound sodium–calcium exchanger (NCX) proteins shape Ca2+ homeostasis in many cell types, thus participating in a wide range of physiological and pathological processes. Determination of the crystal structure of an archaeal NCX (NCX_Mj) paved the way for a thorough and systematic [...] Read more.
The membrane-bound sodium–calcium exchanger (NCX) proteins shape Ca2+ homeostasis in many cell types, thus participating in a wide range of physiological and pathological processes. Determination of the crystal structure of an archaeal NCX (NCX_Mj) paved the way for a thorough and systematic investigation of ion transport mechanisms in NCX proteins. Here, we review the data gathered from the X-ray crystallography, molecular dynamics simulations, hydrogen–deuterium exchange mass-spectrometry (HDX-MS), and ion-flux analyses of mutants. Strikingly, the apo NCX_Mj protein exhibits characteristic patterns in the local backbone dynamics at particular helix segments, thereby possessing characteristic HDX profiles, suggesting structure-dynamic preorganization (geometric arrangements of catalytic residues before the transition state) of conserved α1 and α2 repeats at ion-coordinating residues involved in transport activities. Moreover, dynamic preorganization of local structural entities in the apo protein predefines the status of ion-occlusion and transition states, even though Na+ or Ca2+ binding modifies the preceding backbone dynamics nearby functionally important residues. Future challenges include resolving the structural-dynamic determinants governing the ion selectivity, functional asymmetry and ion-induced alternating access. Taking into account the structural similarities of NCX_Mj with the other proteins belonging to the Ca2+/cation exchanger superfamily, the recent findings can significantly improve our understanding of ion transport mechanisms in NCX and similar proteins. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

2225 KiB  
Review
Multifaceted Roles of ALG-2 in Ca2+-Regulated Membrane Trafficking
by Masatoshi Maki, Terunao Takahara and Hideki Shibata
Int. J. Mol. Sci. 2016, 17(9), 1401; https://doi.org/10.3390/ijms17091401 - 26 Aug 2016
Cited by 41 | Viewed by 9367
Abstract
ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes [...] Read more.
ALG-2 (gene name: PDCD6) is a penta-EF-hand Ca2+-binding protein and interacts with a variety of proteins in a Ca2+-dependent fashion. ALG-2 recognizes different types of identified motifs in Pro-rich regions by using different hydrophobic pockets, but other unknown modes of binding are also used for non-Pro-rich proteins. Most ALG-2-interacting proteins associate directly or indirectly with the plasma membrane or organelle membranes involving the endosomal sorting complex required for transport (ESCRT) system, coat protein complex II (COPII)-dependent ER-to-Golgi vesicular transport, and signal transduction from membrane receptors to downstream players. Binding of ALG-2 to targets may induce conformational change of the proteins. The ALG-2 dimer may also function as a Ca2+-dependent adaptor to bridge different partners and connect the subnetwork of interacting proteins. Full article
(This article belongs to the Special Issue Metalloproteins 2017)
►▼ Show Figures

Graphical abstract

Show export options expand_more Show export options expand_less
Select all
Export citation of selected articles as:
 
Displaying articles 1-17
Back to TopTop