255 results match your criteria breakdown α-crystallin

Dysfunctional Mitochondrial Dynamic and Oxidative Phosphorylation Precedes Cardiac Dysfunction in R120G-αB-Crystallin-Induced Desmin-Related Cardiomyopathy.

J Am Heart Assoc 2020 12 19;9(23):e017195. Epub 2020 Nov 19.

Department of Pathology and Translational Pathobiology Louisiana State University Health Sciences Center Shreveport LA.

Background The mutated α-B-Crystallin (CryAB) mouse model of desmin-related myopathy (DRM) shows an age-dependent onset of pathologic cardiac remodeling and progression of heart failure. CryAB expression in cardiomyocytes affects the mitochondrial spatial organization within the myofibrils, but the molecular perturbation within the mitochondria in the relation of the overall course of the proteotoxic disease remains unclear. Methods and Results CryAB mice show an accumulation of electron-dense aggregates and myofibrillar degeneration associated with the development of cardiac dysfunction. Read More

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December 2020

Cysteine oxidation and disulfide formation in the ribosomal exit tunnel.

Nat Commun 2020 11 4;11(1):5569. Epub 2020 Nov 4.

Institute of Organic Chemistry and Chemical Biology, Center for Biomolecular Magnetic Resonance (BMRZ), Goethe University of Frankfurt, Frankfurt, Germany.

Understanding the conformational sampling of translation-arrested ribosome nascent chain complexes is key to understand co-translational folding. Up to now, coupling of cysteine oxidation, disulfide bond formation and structure formation in nascent chains has remained elusive. Here, we investigate the eye-lens protein γB-crystallin in the ribosomal exit tunnel. Read More

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November 2020

Transient elevation of temperature promotes cross-linking of α-crystallin-client proteins through formation of advanced glycation endproducts: A potential role in presbyopia and cataracts.

Biochem Biophys Res Commun 2020 12 17;533(4):1352-1358. Epub 2020 Oct 17.

Sue Anschutz-Rodgers Eye Center and Department of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA. Electronic address:

The chaperone activity of α-crystallin is important for maintaining the transparency of the human lens. αB-crystallin (αBC) is a long-lived protein in the lens that accumulates chemical modifications during aging. The formation of advanced glycation end products (AGEs) through glycation is one such modification. Read More

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December 2020

An amyloidogenic hexapeptide from the cataract-associated γD-crystallin is a model for the full-length protein and is inhibited by naphthoquinone-tryptophan hybrids.

Int J Biol Macromol 2020 Aug 14;157:424-433. Epub 2020 Apr 14.

Department of Molecular Microbiology and Biotechnology, School of Molecular Cell Biology and Biotechnology, Tel-Aviv University, 69978 Tel Aviv, Israel; The Interdisciplinary Sagol School of Neurosciences, Tel-Aviv University, 69978 Tel Aviv, Israel. Electronic address:

The eye lens is rich in proteins called crystallins, whose native conformation is crucial for preserving its transparency. With aging, crystallins may be exposed to environmental changes, which could lead to their aggregation and eventually to cataract development. Human γD-crystallin, among the most abundantly expressed γ-crystallins in the lens, was shown to form amyloid aggregates under denaturing conditions in vitro. Read More

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Lysine malonylation and propionylation are prevalent in human lens proteins.

Exp Eye Res 2020 01 31;190:107864. Epub 2019 Oct 31.

Sue Anschutz-Rodgers Eye Center and Department of Ophthalmology, School of Medicine, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA. Electronic address:

Acylated lysine residues represent major chemical modifications in proteins. We investigated the malonylation and propionylation of lysine residues (MalK, PropK) in the proteins of aging human lenses. Western blot results showed that the two modifications are present in human lens proteins. Read More

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January 2020

Glucoselysine is derived from fructose and accumulates in the eye lens of diabetic rats.

J Biol Chem 2019 11 8;294(46):17326-17338. Epub 2019 Oct 8.

Laboratory of Food and Regulation Biology, Graduate School of Bioscience, Tokai University, 9-1-1 Toroku, Kumamoto, Higashi-ku, Kumamoto 862-0970, Japan

Prolonged hyperglycemia generates advanced glycation end-products (AGEs), which are believed to be involved in the pathogenesis of diabetic complications. In the present study, we developed a polyclonal antibody against fructose-modified proteins (Fru-P antibody) and identified its epitope as glucoselysine (GL) by NMR and LC-electrospray ionization (ESI)- quadrupole TOF (QTOF) analyses and evaluated its potential role in diabetes sequelae. Although the molecular weight of GL was identical to that of fructoselysine (FL), GL was distinguishable from FL because GL was resistant to acid hydrolysis, which converted all of the FLs to furosine. Read More

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November 2019

Analysis of Glutamine Deamidation: Products, Pathways, and Kinetics.

Anal Chem 2019 10 25;91(20):13032-13038. Epub 2019 Sep 25.

Department of Chemistry , University of California , Riverside , California 92521 , United States.

Spontaneous chemical modifications play an important role in human disease and aging at the molecular level. Deamidation and isomerization are known to be among the most prevalent chemical modifications in long-lived human proteins and are implicated in a growing list of human pathologies, but the relatively minor chemical change associated with these processes has presented a long standing analytical challenge. Although the adoption of high-resolution mass spectrometry has greatly aided the identification of deamidation sites in proteomic studies, isomerization (and the isomeric products of deamidation) remain exceptionally challenging to characterize. Read More

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October 2019

Synthesis, Self-Assembly and Characterization of Tandem Triblock BPOSS-PDI-X Shape Amphiphiles.

Molecules 2019 Jun 4;24(11). Epub 2019 Jun 4.

State Key Laboratory for Modification of Chemical Fibers and Polymer Materials and College of Material Science and Engineering, Center for Advanced Low-Dimension Materials, Donghua University, Shanghai 201620, China.

In this article, we report the facile synthesis, self-assembly, and characterization of shape amphiphiles (BPOSS-PDI-X) based on isobutyl-functionalized polyhedral oligomeric silsesquioxane (BPOSS), perylene tetracarboxylic diimide (PDI), and (60)fullerene (C) moieties. Firstly, an asymmetrically functionalized diblock shape amphiphile precursor (BPOSS-PDI-OH) was obtained through the one-pot reaction between perylene-3,4,9,10-tetracarboxylic dianhydride and two different amines, namely BPOSS-NH and 3-amino-1-propanol. It was further conjugated with C-COOH to give a tri-block shape amphiphile (BPOSS-PDI-C). Read More

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Biophysical analyses and functional implications of the interaction between Heat Shock Protein 27 and antibodies to HSP27.

Biochim Biophys Acta Gen Subj 2019 10 25;1863(10):1536-1546. Epub 2019 May 25.

Department of Cardiac Sciences, Libin Cardiovascular Institute of Alberta, Cumming School of Medicine, University of Calgary, Calgary, Alberta T2N 1N4, Canada. Electronic address:

Heat Shock Protein 27 (HSP27) is a small molecular chaperone that reduces the development of atherosclerosis by lowering plasma cholesterol levels as well as inflammation. Human studies show an inverse correlation between atherosclerotic burden and HSP27 expression, and are supported by murine models in which augmenting HSP27 levels curbs experimental atherogenesis. Natural HSP27 auto-antibodies (AAb) are found in human plasma, however their role in modulating the athero-protective effects of HSP27 is unknown. Read More

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October 2019

3-Hydroxykynurenine bound to eye lens proteins induces oxidative modifications in crystalline proteins through a type I photosensitizing mechanism.

Free Radic Biol Med 2019 09 22;141:103-114. Epub 2019 May 22.

Departamento de Química Física, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago, Chile.

Photosensitized reactions mediated by endogenous chromophores have been associated with the etiology of age-related cataract disease. Endogenous chromophores such as 3-hydroxykynurenine (3OHKN) can be found in both free form, and bound to crystallin proteins. However, their efficiency in generating photo-induced oxidative modifications on eye lens proteins is not completely understood. Read More

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September 2019

Small heat shock protein genes of the green algae Closterium ehrenbergii: Cloning and differential expression under heat and heavy metal stresses.

Environ Toxicol 2019 Sep 16;34(9):1013-1024. Epub 2019 May 16.

Department of Biotechnology, Sangmyung University, Seoul, South Korea.

The freshwater green algae Closterium ehrenbergii has been considered as a model for eco-toxicological assessment in aquatic systems. Heat shock proteins (HSPs) are a class of highly conserved proteins produced in all living organisms, which participate in environmental stress responses. In the present study, we determined the cDNA sequences of small heat shock protein 10 (sHSP10) and sHSP17. Read More

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September 2019

The absence of SIRT3 and SIRT5 promotes the acetylation of lens proteins and improves the chaperone activity of α-crystallin in mouse lenses.

Exp Eye Res 2019 05 5;182:1-9. Epub 2019 Mar 5.

Sue Anschutz-Rodgers Eye Center and Department of Ophthalmology, School of Medicine, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA; Department of Pharmaceutical Sciences, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of Colorado, Anschutz Medical Campus, Aurora, CO, 80045, USA. Electronic address:

Acetylation of lysine residues occurs in lens proteins. Previous studies have shown an improvement in the chaperone activity of αA-crystallin upon acetylation. Sirtuins are NAD-dependent enzymes that can deacylate proteins. Read More

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Succinylation Is a Gain-of-Function Modification in Human Lens αB-Crystallin.

Biochemistry 2019 03 20;58(9):1260-1274. Epub 2019 Feb 20.

Acylation of lysine residues is a common post-translational modification of cellular proteins. Here, we show that lysine succinylation, a type of acylation, occurs in human lens proteins. All of the major crystallins exhibited N-succinyllysine (SuccK) residues. Read More

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O-GlcNAc Site Mapping by Using a Combination of Chemoenzymatic Labeling, Copper-Free Click Chemistry, Reductive Cleavage, and Electron-Transfer Dissociation Mass Spectrometry.

Anal Chem 2019 02 4;91(4):2620-2625. Epub 2019 Feb 4.

Department of Biological Chemistry , The Johns Hopkins University School of Medicine , Baltimore , Maryland 21205 , United States.

As a dynamic post-translational modification, O-linked β- N-acetylglucosamine ( O-GlcNAc) modification (i.e., O-GlcNAcylation) of proteins regulates many biological processes involving cellular metabolism and signaling. Read More

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February 2019

Effects of glycation on human γd-crystallin proteins by different glycation-inducing agents.

Int J Biol Macromol 2018 Oct 24;118(Pt A):442-451. Epub 2018 Jun 24.

Department of Chemical Engineering, National Taiwan University, Taipei 10617, Taiwan. Electronic address:

Human γd-crystallin (Hγd-crystallin), a major protein component of the human eye lens, is associated with the development of juvenile- and mature-onset cataracts. Evidence suggests that nonenzymatic protein glycation plays an important role in the aetiology of cataract and diabetic sequelae. This research compared the effects of various glycation modifiers on Hγd-crystallin aggregation, by treating samples of Hγd-crystallin with ribose, galactose, or methylglyoxal using several biophysical techniques. Read More

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October 2018

Quantification of thioether-linked glutathione modifications in human lens proteins.

Exp Eye Res 2018 10 4;175:83-89. Epub 2018 Jun 4.

Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, TN, USA. Electronic address:

Dehydroalanine (DHA) and dehydrobutyrine (DHB) intermediates, formed through β-elimination, induce protein irreversible glutathionylation and protein-protein crosslinking in human lens fiber cells. In total, irreversible glutathionylation was detected on 52 sites including cysteine, serine and threonine residues in 18 proteins in human lenses. In this study, the levels of GSH modification on three serine residues and four cysteine residues located in seven different lens proteins isolated from different regions and different aged lenses were quantified. Read More

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October 2018

Desmin Phosphorylation Triggers Preamyloid Oligomers Formation and Myocyte Dysfunction in Acquired Heart Failure.

Circ Res 2018 05 26;122(10):e75-e83. Epub 2018 Feb 26.

Johns Hopkins School of Medicine, Baltimore, MD (P.P.R., P.D., Y.W., C.A.F., M.G.P., G.F.T., N.P., G.A.)

Rationale: Disrupted proteostasis is one major pathological trait that heart failure (HF) shares with other organ proteinopathies, such as Alzheimer and Parkinson diseases. Yet, differently from the latter, whether and how cardiac preamyloid oligomers (PAOs) develop in acquired forms of HF is unclear.

Objective: We previously reported a rise in monophosphorylated, aggregate-prone desmin in canine and human HF. Read More

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Synthesis and biological evaluation of anti-cancer agents that selectively inhibit Her2 over-expressed breast cancer cell growth via down-regulation of Her2 protein.

Bioorg Med Chem Lett 2018 02 12;28(4):727-731. Epub 2018 Jan 12.

Department of Chemistry, Center for Gene Regulation in Health and Disease, College of Sciences and Health Professions, Cleveland State University, 2121 Euclid Ave., Cleveland, OH 44115, USA. Electronic address:

Compound JCC76 selectively inhibited the proliferation of human epidermal growth factor 2 (Her2) over-expressed breast cancer cells. In the current study, a ligand based structural optimization was performed to generate new analogs, and we identified derivatives 16 and 17 that showed improved activity and selectivity against Her2 positive breast cancer cells. A structure activity relationship (SAR) was summarized. Read More

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February 2018

DehydroalanylGly, a new post translational modification resulting from the breakdown of glutathione.

Biochim Biophys Acta Gen Subj 2018 Apr 6;1862(4):907-913. Epub 2018 Jan 6.

Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2500, Australia.

Background: The human body contains numerous long-lived proteins which deteriorate with age, typically by racemisation, deamidation, crosslinking and truncation. Previously we elucidated one reaction responsible for age-related crosslinking, the spontaneous formation of dehydroalanine (DHA) intermediates from phosphoserine and cysteine. This resulted in non-disulphide covalent crosslinks. Read More

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The Major Chromophore Arising from Glucose Degradation and Oxidative Stress Occurrence during Lens Proteins Glycation Induced by Glucose.

Molecules 2017 Dec 22;23(1). Epub 2017 Dec 22.

Laboratorio de Química Biológica, Facultad de Química, Pontificia Universidad Católica de Chile, Santiago 7820436, Chile.

Glucose autoxidation has been proposed as a key reaction associated with deleterious effects induced by hyperglycemia in the eye lens. Little is known about chromophores generated during glucose autoxidation. In this study, we analyzed the effect of oxidative and dicarbonyl stress in the generation of a major chromophore arising from glucose degradation (GDC) and its association with oxidative damage in lens proteins. Read More

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December 2017

Dimerization and oxidation of tryptophan in UV-A photolysis sensitized by kynurenic acid.

Free Radic Biol Med 2017 12 9;113:372-384. Epub 2017 Oct 9.

International Tomography Center SB RAS, Institutskaya str. 3A, 630090 Novosibisrk, Russia; Novosibirsk State University, Pirogova str. 2, 630090 Novosibisrk, Russia.

Photoinduced generation of radicals in the eye lens may play an important role in the modification of proteins leading to their coloration, aggregation, and insolubilization. The radicals can be formed via the reactions of photoexcited endogenous chromophores of the human lens with lens proteins, in particular with tryptophan residues. In the present work we studied the reactions induced by UV-A (315-400nm) light between kynurenic acid (KNA), an effective photosensitizer present in the human lens, and N-acetyl-L-tryptophan (NTrpH) under aerobic and anaerobic conditions. Read More

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December 2017

Exposure to cocaine and its main metabolites altered the protein profile of zebrafish embryos.

Environ Pollut 2018 Jan 6;232:603-614. Epub 2017 Oct 6.

Department of Biosciences, University of Milan, via Celoria 26, I-20133 Milan, Italy.

Illicit drugs have been identified as emerging aquatic pollutants because of their widespread presence in freshwaters and potential toxicity towards aquatic organisms. Among illicit drug residues, cocaine (COC) and its main metabolites, namely benzoylecgonine (BE) and ecgonine methyl ester (EME), are commonly detected in freshwaters worldwide at concentration that can induce diverse adverse effects to non-target organisms. However, the information of toxicity and mechanisms of action (MoA) of these drugs, mainly of COC metabolites, to aquatic species is still fragmentary and inadequate. Read More

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January 2018

Effect of Green Tea Polyphenol Epigallocatechin-3-gallate on the Aggregation of αA(66-80) Peptide, a Major Fragment of αA-crystallin Involved in Cataract Development.

Curr Eye Res 2017 10 19;42(10):1368-1377. Epub 2017 Jun 19.

a Department of Biotechnology , Central University of Rajasthan , NH-8 Bandarsindri, Kishangarh Ajmer , Rajasthan , India.

Purpose: Crystallin is a major protein present in eye lens. Peptide fragment αA(66-80) derived from αA-crystallin possesses high aggregation propensity and forms amyloid-like structures. αA(66-80) aggregates are known to interact with soluble crystallins and destabilize native structures that subsequently undergo aggregation. Read More

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October 2017

Hotspots of age-related protein degradation: the importance of neighboring residues for the formation of non-disulfide crosslinks derived from cysteine.

Biochem J 2017 07 11;474(14):2475-2487. Epub 2017 Jul 11.

Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2500, Australia.

Over time, the long-lived proteins that are present throughout the human body deteriorate. Typically, they become racemized, truncated, and covalently cross-linked. One reaction responsible for age-related protein cross-linking in the lens was elucidated recently and shown to involve spontaneous formation of dehydroalanine (DHA) intermediates from phosphoserine. Read More

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Does oxidative stress play any role in diabetic cataract formation? ----Re-evaluation using a thioltransferase gene knockout mouse model.

Exp Eye Res 2017 08 1;161:36-42. Epub 2017 Jun 1.

School of Veterinary Medicine and Biomedical Sciences, Lincoln, NE, USA; Redox Biology Center, University of Nebraska-Lincoln, Lincoln, NE, USA; Department of Ophthalmology, University of Nebraska-Medical Center, Omaha, NE, USA. Electronic address:

Oxidative stress is a known risk factor in senile cataract formation. In recent years, it has been suggested that oxidation may also be associated with cataract induced by hyperglycemia, but this concept has not been well examined or validated. Since thioltransferase (TTase) is one of the key enzymes that regulates redox homeostasis and protects against oxidative stress in the lens, we have used TTase gene knockout (KO) mice as a model to examine this new concept. Read More

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Prevention and reversal of selenite-induced cataracts by N-acetylcysteine amide in Wistar rats.

BMC Ophthalmol 2017 Apr 26;17(1):54. Epub 2017 Apr 26.

Department of Chemistry, Missouri University of Science and Technology, Rolla, MO, 65409, USA.

Background: The present study sought to evaluate the efficacy of N-acetylcysteine amide (NACA) eye drops in reversing the cataract formation induced by sodium selenite in male Wistar rat pups.

Methods: Forty male Wistar rat pups were randomly divided into a control group, an N-acetylcysteine amide-only group, a sodium selenite-induced cataract group, and a NACA-treated sodium selenite-induced cataract group. Sodium selenite was injected intraperitoneally on postpartum day 10, whereas N-acetylcysteine amide was injected intraperitoneally on postpartum days 9, 11, and 13 in the respective groups. Read More

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Protective Effects of Acetylation on the Pathological Reactions of the Lens Crystallins with Homocysteine Thiolactone.

PLoS One 2016 5;11(10):e0164139. Epub 2016 Oct 5.

Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.

Various post-translational lens crystallins modifications result in structural and functional insults, contributing to the development of lens opacity and cataract disorders. Lens crystallins are potential targets of homocysteinylation, particularly under hyperhomocysteinemia which has been indicated in various eye diseases. Since both homocysteinylation and acetylation primarily occur on protein free amino groups, we applied different spectroscopic methods and gel mobility shift analysis to examine the possible preventive role of acetylation against homocysteinylation. Read More

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CpG site methylation in CRYAA promoter affect transcription factor Sp1 binding in human lens epithelial cells.

BMC Ophthalmol 2016 Aug 9;16:141. Epub 2016 Aug 9.

Department of Ophthalmology, Eye and ENT Hospital of Fudan University, 83 FenYang Road, Shanghai, 200031, People's Republic of China.

Background: Age-related cataract (ARC) is the leading cause of visual impairment worldwide, and α-crystallin (CRYAA) is the predominant structural protein involved in the maintenance of lens clarity and refractive properties. We previously demonstrated that CRYAA genes undergo epigenetic repression in the lens epithelia in ARC. We further analyze the underlying mechanism in the current study. Read More

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Protection of human γB-crystallin from UV-induced damage by epigallocatechin gallate: spectroscopic and docking studies.

Mol Biosyst 2016 08;12(9):2901-9

Department of Chemistry, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.

The transparency of the human eye lens depends on the solubility and stability of the structural proteins of the eye lens, the crystallins. Although the mechanism of cataract formation is still unclear, it is believed to involve protein misfolding and/or aggregation of proteins due to the influence of several external factors such as ultraviolet (UV) radiation, low pH, temperature and exposure to chemical agents. In this article, we report the study of UV induced photo-damage (under oxidative stress) of recombinant human γB-crystallin in vitro in the presence of the major green tea polyphenol, (-)-epigallocatechin gallate (EGCG). Read More

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Expression and localization of the Xenopus laevis small heat shock protein, HSPB6 (HSP20), in A6 kidney epithelial cells.

Comp Biochem Physiol A Mol Integr Physiol 2016 11 21;201:12-21. Epub 2016 Jun 21.

Department of Biology, University of Waterloo, Waterloo, ON N2L 3G1, Canada. Electronic address:

Small heat shock proteins (sHSPs) are molecular chaperones that bind to unfolded protein, inhibit the formation of toxic aggregates and facilitate their refolding and/or degradation. Previously, the only sHSPs that have been studied in detail in the model frog system, Xenopus laevis, were members of the HSP30 family and HSPB1 (HSP27). We now report the analysis of X. Read More

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November 2016