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Pesquisa : D12.776.306.366.100.149 [Categoria DeCS]
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[PMID]:29338044
[Au] Autor:Andley UP; Tycksen E; McGlasson-Naumann BN; Hamilton PD
[Ad] Endereço:Department of Ophthalmology and Visual Sciences, Washington University School of Medicine, St. Louis, Missouri, United States of America.
[Ti] Título:Probing the changes in gene expression due to α-crystallin mutations in mouse models of hereditary human cataract.
[So] Source:PLoS One;13(1):e0190817, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The mammalian eye lens expresses a high concentration of crystallins (α, ß and γ-crystallins) to maintain the refractive index essential for lens transparency. Crystallins are long-lived proteins that do not turnover throughout life. The structural destabilization of crystallins by UV exposure, glycation, oxidative stress and mutations in crystallin genes leads to protein aggregation and development of cataracts. Several destabilizing mutations in crystallin genes are linked with human autosomal dominant hereditary cataracts. To investigate the mechanism by which the α-crystallin mutations Cryaa-R49C and Cryab-R120G lead to cataract formation, we determined whether these mutations cause an altered expression of specific transcripts in the lens at an early postnatal age by RNA-seq analysis. Using knock-in mouse models previously generated in our laboratory, in the present work, we identified genes that exhibited altered abundance in the mutant lenses, including decreased transcripts for Clic5, an intracellular water channel in Cryaa-R49C heterozygous mutant lenses, and increased transcripts for Eno1b in Cryab-R120G heterozygous mutant lenses. In addition, RNA-seq analysis revealed increased histones H2B, H2A, and H4 gene expression in Cryaa-R49C mutant lenses, suggesting that the αA-crystallin mutation regulates histone expression via a transcriptional mechanism. Additionally, these studies confirmed the increased expression of histones H2B, H2A, and H4 by proteomic analysis of Cryaa-R49C knock-in and Cryaa;Cryab gene knockout lenses reported previously. Taken together, these findings offer additional insight into the early transcriptional changes caused by Cryaa and Cryab mutations associated with autosomal dominant human cataracts, and indicate that the transcript levels of certain genes are affected by the expression of mutant α-crystallin in vivo.
[Mh] Termos MeSH primário: Catarata/genética
Mutação
Cadeia A de alfa-Cristalina/genética
Cadeia B de alfa-Cristalina/genética
[Mh] Termos MeSH secundário: Animais
Carboxipeptidases/genética
Carboxipeptidases/metabolismo
Catarata/metabolismo
Canais de Cloreto/genética
Canais de Cloreto/metabolismo
Modelos Animais de Doenças
Expressão Gênica
Técnicas de Introdução de Genes
Histonas/genética
Histonas/metabolismo
Seres Humanos
Cristalino/metabolismo
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Mutantes
Camundongos Transgênicos
Proteínas/genética
Proteínas/metabolismo
Proteômica
Proteínas Repressoras/genética
Proteínas Repressoras/metabolismo
Cadeia A de alfa-Cristalina/metabolismo
Cadeia B de alfa-Cristalina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Aebp1 protein, mouse); 0 (CLIC5 protein, mouse); 0 (Chloride Channels); 0 (Cryab protein, mouse); 0 (Histones); 0 (Proteins); 0 (Repressor Proteins); 0 (alpha-Crystallin A Chain); 0 (alpha-Crystallin B Chain); 0 (vig1 protein, mouse); EC 3.4.- (Carboxypeptidases)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180213
[Lr] Data última revisão:
180213
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0190817


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[PMID]:28935373
[Au] Autor:Chaves JM; Gupta R; Srivastava K; Srivastava O
[Ad] Endereço:Department of Optometry and Vision Science, University of Alabama at Birmingham, Birmingham, AL 35294, United States.
[Ti] Título:Human alpha A-crystallin missing N-terminal domain poorly complexes with filensin and phakinin.
[So] Source:Biochem Biophys Res Commun;494(1-2):402-408, 2017 Dec 09.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The aim of this study was to determine relative importance of N-terminal domain and C-terminal extension of αA-crystallin during their in vitro complex formation with phakinin and filensin (the two lens-specific intermediate filament [IF] proteins). Cloned phakinin, filensin and vimentin were purified under a denaturing conditions by consecutive DEAE-cellulose-, hydroxyapatite- and Sephadex G-75-column chromatographic methods. WTαA-crystallin, αA-NT (N-terminal domain [residue number 1-63])-deleted and αA-CT (C-terminal terminal extension [residue number 140-173]-deleted), were cloned in pET 100 TOPO vector, expressed in BL-21 (DE3) cells using 1% IPTG, and purified using a Ni -affinity column. The following two in vitro methods were used to determine complex formation of WT-αA, αA-NT, or αA-CT with phakinin, filensin or both phakinin plus filensin together: an ultracentrifugation sedimentation (centrifugation at 80,000 × g for 30 min at 20 °C) followed by SDS-PAGE analysis, and an electron microscopic analysis. In the first method, the individual control proteins (WT-αA, αA-NT and αA-CT crystallin species) remained in the supernatant fractions whereas phakinin, filensin, and vimentin were recovered in the pellet fractions. On complex formation by individual WT-αA-, αA-NT or αA-CT-species with filensin, phakinin or both phakinin and filensin, WT-αA and αA-CT were recovered in the pellet fraction with phakinin, filensin or both filensin and phakinin, whereas αA-NT remained mostly in the supernatant, suggesting its poor complex formation property. EM-studies showed filamentous structure formation between WT-αA and αA-CT with phakinin or filensin, or with both filensin and phakinin together but relatively poor filamentous structures with αA-NT. Together, the results suggest that the N-terminal domain of αA-crystallin is required during in vitro complex formation with filensin and phakinin.
[Mh] Termos MeSH primário: Proteínas do Olho/metabolismo
Vetores Genéticos/química
Proteínas de Filamentos Intermediários/metabolismo
Cadeia A de alfa-Cristalina/metabolismo
[Mh] Termos MeSH secundário: Sítios de Ligação
Clonagem Molecular
Escherichia coli/genética
Escherichia coli/metabolismo
Proteínas do Olho/genética
Proteínas do Olho/ultraestrutura
Expressão Gênica
Vetores Genéticos/metabolismo
Seres Humanos
Proteínas de Filamentos Intermediários/genética
Proteínas de Filamentos Intermediários/ultraestrutura
Filamentos Intermediários/metabolismo
Filamentos Intermediários/ultraestrutura
Cristalino/metabolismo
Cristalino/ultraestrutura
Microscopia Eletrônica
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Proteínas Recombinantes/ultraestrutura
Cadeia A de alfa-Cristalina/genética
Cadeia A de alfa-Cristalina/ultraestrutura
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eye Proteins); 0 (Intermediate Filament Proteins); 0 (Recombinant Proteins); 0 (alpha-Crystallin A Chain); 0 (filensin); 0 (phakinin)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171108
[Lr] Data última revisão:
171108
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170923
[St] Status:MEDLINE


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[PMID]:28720498
[Au] Autor:Mallik PK; Shi H; Pande J
[Ad] Endereço:Department of Chemistry, University at Albany, State University of New York, 1400 Washington Avenue, Albany 12222, N.Y, United States.
[Ti] Título:RNA aptamers targeted for human αA-crystallin do not bind αB-crystallin, and spare the α-crystallin domain.
[So] Source:Biochem Biophys Res Commun;491(2):423-428, 2017 Sep 16.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The molecular chaperones, α-crystallins, belong to the small heat shock protein (sHSP) family and prevent the aggregation and insolubilization of client proteins. Studies in vivo have shown that the chaperone activity of the α-crystallins is raised or lowered in various disease states. Therefore, the development of tools to control chaperone activity may provide avenues for therapeutic intervention, as well as enable a molecular understanding of chaperone function. The major human lens α-crystallins, αA- (HAA) and αB- (HAB), share 57% sequence identity and show similar activity towards some clients, but differing activities towards others. Notably, both crystallins contain the "α-crystallin domain" (ACD, the primary client binding site), like all other members of the sHSP family. Here we show that RNA aptamers selected for HAA, in vitro, exhibit specific affinity to HAA but do not bind HAB. Significantly, these aptamers also exclude the ACD. This study thus demonstrates that RNA aptamers against sHSPs can be designed that show high affinity and specificity - yet exclude the primary client binding region - thereby facilitating the development of RNA aptamer-based therapeutic intervention strategies.
[Mh] Termos MeSH primário: Aptâmeros de Nucleotídeos/química
Cadeia A de alfa-Cristalina/química
Cadeia B de alfa-Cristalina/química
[Mh] Termos MeSH secundário: Aptâmeros de Nucleotídeos/síntese química
Sequência de Bases
Sítios de Ligação
Expressão Gênica
Seres Humanos
Meliteno/química
Octoxinol/química
Ligação Proteica
Domínios e Motivos de Interação entre Proteínas
Proteínas Recombinantes/química
Técnica de Seleção de Aptâmeros
Tensoativos/química
Cadeia A de alfa-Cristalina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Aptamers, Nucleotide); 0 (Recombinant Proteins); 0 (Surface-Active Agents); 0 (alpha-Crystallin A Chain); 0 (alpha-Crystallin B Chain); 20449-79-0 (Melitten); 9002-93-1 (Octoxynol)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170720
[St] Status:MEDLINE


  4 / 253 MEDLINE  
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[PMID]:28527593
[Au] Autor:Ray NJ; Hall D; Carver JA
[Ad] Endereço:Research School of Chemistry, The Australian National University, Acton, ACT 2601, Australia.
[Ti] Título:A structural and functional study of Gln147 deamidation in αA-crystallin, a site of modification in human cataract.
[So] Source:Exp Eye Res;161:163-173, 2017 Aug.
[Is] ISSN:1096-0007
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Deamidation of Glu147 in human αA-crystallin is common in aged cataractous lenses (Hains and Truscott, Invest. Ophthalmol. Vis. Sci. 2010, 51, 3107). Accordingly, this modification may have a causative effect in cataract. αA-crystallin is a small heat-shock molecular chaperone protein that prevents aggregation of proteins and is the principal defence against crystallin unfolding and aggregation in the ageing lens. Deamidated Q147E αA-crystallin was structurally characterised using a variety of spectroscopic and biophysical methods, including NMR, circular dichroism and fluorescence spectroscopy and dynamic light scattering. The effect of Glu147 deamidation on αA-crystallin in vitro chaperone ability was determined for a variety of aggregating proteins. Compared to the wild type protein, Q147E αA-crystallin generally exhibited slightly reduced chaperone ability and a small loss of overall structure in its central α-crystallin domain while also showing significantly enhanced thermal stability and a tendency to form slightly larger oligomers. As αA-crystallin is the major lens protein, even a small loss of function could combine with other sources of age-related damage to the crystallins to contribute to lens opacification.
[Mh] Termos MeSH primário: Catarata/metabolismo
Glutamina/química
Chaperonas Moleculares/metabolismo
Cadeia A de alfa-Cristalina/metabolismo
[Mh] Termos MeSH secundário: Dicroísmo Circular
Seres Humanos
Ressonância Magnética Nuclear Biomolecular
Ligação Proteica
Processamento de Proteína Pós-Traducional
Estabilidade Proteica
Espectrometria de Fluorescência
Relação Estrutura-Atividade
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Molecular Chaperones); 0 (alpha-Crystallin A Chain); 0RH81L854J (Glutamine)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170821
[Lr] Data última revisão:
170821
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170522
[St] Status:MEDLINE


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[PMID]:28475701
[Au] Autor:Yuan L; Yao H; Xu Y; Chen M; Deng J; Song Y; Sui T; Wang Y; Huang Y; Li Z; Lai L
[Ad] Endereço:Jilin Provincial Key Laboratory of Animal Embryo Engineering, Institute of Zoonosis, College of Animal Science, Jilin University, Changchun, China.
[Ti] Título:CRISPR/Cas9-Mediated Mutation of αA-Crystallin Gene Induces Congenital Cataracts in Rabbits.
[So] Source:Invest Ophthalmol Vis Sci;58(6):BIO34-BIO41, 2017 May 01.
[Is] ISSN:1552-5783
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Purpose: The present study aimed to investigate the role of the αA-crystallin gene in inducing congenital cataracts in rabbits and to construct a novel animal model for characterization and pathologic analysis of congenital cataracts for future research. Methods: We generated αA-crystallin gene knockout rabbits with congenital cataracts by coinjection of Cas9 mRNA and sgRNA into zygotes. Cataract phenotypes were investigated in a repeated study of 19 F0-generation and 11 F1-generation rabbits with αA-crystallin gene mutations. Heritability was analyzed by PCR, sequencing, slim lamp, hematoxylin eosin staining, immunohistochemistry, and Western blot. Results: We found αA-crystallin gene mutations in all 19 F0-generation pups (100%) with indel mutations in the αA-crystallin gene ranging from 3 to 52 bp. Off-target assay revealed that none of the potential off-target sites exhibited mutations, demonstrating that off-target mutagenesis was not induced by cytoplasmic microinjection of in vitro-transcribed Cas9 mRNA. Slim lamp assay revealed that 15 of 19 live pups (78.9%) exhibited typical phenotypes, including congenital cataracts, microphthalmia, obscurity, and early atrophy of the lens, and failed differentiation of lens fibers. Histologic hematoxylin and eosin staining showed that αA-crystallin gene knockout rabbits exhibited smaller lenses. Production of the αA-crystallin protein was determined to be dramatically reduced in αA-crystallin gene knockout rabbits. We induced αA-crystallin gene mutations and phenotypes in F1-generation rabbits. Conclusions: Our data suggest that CRISPR/Cas9-mediated mutation of the αA-crystallin gene in rabbits recapitulates phenotypes of congenital cataracts, microphthalmia, obscurity, and early atrophy of the lens, and failed differentiation of lens fibers. These findings suggest the possibility of a new animal model of congenital cataracts, which should be used to further investigate the association between mutations in αA-crystallin gene and congenital cataracts in humans.
[Mh] Termos MeSH primário: Catarata/genética
DNA/genética
Cristalino/metabolismo
Mutação
Cadeia A de alfa-Cristalina/genética
[Mh] Termos MeSH secundário: Animais
Western Blotting
Catarata/congênito
Catarata/metabolismo
Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas
Análise Mutacional de DNA
Modelos Animais de Doenças
Imuno-Histoquímica
Fenótipo
Reação em Cadeia da Polimerase
Coelhos
Cadeia A de alfa-Cristalina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (alpha-Crystallin A Chain); 9007-49-2 (DNA)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170506
[St] Status:MEDLINE
[do] DOI:10.1167/iovs.16-21287


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[PMID]:28320295
[Au] Autor:Tikhomirova TS; Selivanova OM; Galzitskaya OV
[Ad] Endereço:Institute of Protein Research, Russian Academy of Sciences, Pushchino, Moscow Region, 142290, Russia. ogalzit@vega.protres.ru.
[Ti] Título:α-Crystallins Are Small Heat Shock Proteins: Functional and Structural Properties.
[So] Source:Biochemistry (Mosc);82(2):106-121, 2017 Feb.
[Is] ISSN:1608-3040
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:During its life cycle, a cell can be subjected to various external negative effects. Many proteins provide cell protection, including small heat shock proteins (sHsp) that have chaperone-like activity. These proteins have several important functions involving prevention of apoptosis and retention of cytoskeletal integrity; also, sHsp take part in the recovery of enzyme activity. The action mechanism of sHsp is based on the binding of hydrophobic regions exposed to the surface of a molten globule. α-Crystallins presented in chordate cells as two αA- and αB-isoforms are the most studied small heat shock proteins. In this review, we describe the main functions of α-crystallins, features of their secondary and tertiary structures, and examples of their partners in protein-protein interactions.
[Mh] Termos MeSH primário: Proteínas de Choque Térmico/química
Cadeia A de alfa-Cristalina/química
Cadeia B de alfa-Cristalina/química
[Mh] Termos MeSH secundário: Animais
Apoptose/fisiologia
Citoesqueleto/química
Citoesqueleto/metabolismo
Proteínas de Choque Térmico/metabolismo
Seres Humanos
Domínios Proteicos
Estrutura Secundária de Proteína
Relação Estrutura-Atividade
Cadeia A de alfa-Cristalina/metabolismo
Cadeia B de alfa-Cristalina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Heat-Shock Proteins); 0 (alpha-Crystallin A Chain); 0 (alpha-Crystallin B Chain)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170322
[Lr] Data última revisão:
170322
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1134/S0006297917020031


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[PMID]:27905156
[Au] Autor:Aki K; Okamura E
[Ad] Endereço:Faculty of Pharmaceutical Sciences, Himeji Dokkyo University, 7-2-1 Kamiohno, Himeji, 670-8524, Japan.
[Ti] Título:Kinetics of the competitive reactions of isomerization and peptide bond cleavage at l-α- and d-ß-aspartyl residues in an αA-crystallin fragment.
[So] Source:J Pept Sci;23(1):28-37, 2017 Jan.
[Is] ISSN:1099-1387
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:d-ß-aspartyl (Asp) residue has been found in a living body such as aged lens crystallin, although l-α-amino acids are constituents in natural proteins. Isomerization from l-α- to d-ß-Asp probably modulates structures to affect biochemical reactions. At Asp residue, isomerization and peptide bond cleavage compete with each other. To gain insight into how fast each reaction proceeds, the analysis requires the consideration of both pathways simultaneously and independently. No information has been provided, however, about these competitive processes because each reaction has been studied separately. The contribution of Asp isomers to the respective pathways has still been veiled. In this work, the two competitive reactions, isomerization and spontaneous peptide bond cleavage at Asp residue, were simultaneously observed and compared in an αA-crystallin fragment, S LFRTVLD SG containing l-α- and d-ß-Asp58 isomers. The kinetics showed that the formation of l- and d-succinimide (Suc) intermediate, as a first step of isomerization, was comparable at l-α- and d-ß-Asp. Although l-Suc was converted to l-ß-Asp, d-Suc was liable to return to the original d-ß-Asp, the reverse reaction marked enough to consider d-ß-Asp as apparently stable. d-ß-Asp was also resistant to the peptide bond cleavage. Such apparent less reactivity is probably the reason for gradual and abnormal accumulation of d-ß-Asp in a living body under physiological conditions. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
[Mh] Termos MeSH primário: Ácido Aspártico/química
Oligopeptídeos/química
Cadeia A de alfa-Cristalina/química
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Fluorenos/química
Seres Humanos
Cinética
Cristalino/química
Oligopeptídeos/síntese química
Estabilidade Proteica
Proteólise
Estereoisomerismo
Succinimidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fluorenes); 0 (Oligopeptides); 0 (Succinimides); 0 (alpha-Crystallin A Chain); 10X90O3503 (succinimide); 30KYC7MIAI (Aspartic Acid)
[Em] Mês de entrada:1703
[Cu] Atualização por classe:170309
[Lr] Data última revisão:
170309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE
[do] DOI:10.1002/psc.2945


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[PMID]:27770023
[Au] Autor:Wu SY; Zou P; Fuller AW; Mishra S; Wang Z; Schey KL; Mchaourab HS
[Ad] Endereço:From the Departments of Molecular Physiology and Biophysics and.
[Ti] Título:Expression of Cataract-linked γ-Crystallin Variants in Zebrafish Reveals a Proteostasis Network That Senses Protein Stability.
[So] Source:J Biol Chem;291(49):25387-25397, 2016 Dec 02.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The refractivity and transparency of the ocular lens is dependent on the stability and solubility of the crystallins in the fiber cells. A number of mutations of lens crystallins have been associated with dominant cataracts in humans and mice. Of particular interest were γB- and γD-crystallin mutants linked to dominant cataracts in mouse models. Although thermodynamically destabilized and aggregation-prone, these mutants were found to have weak affinity to the resident chaperone α-crystallin in vitro To better understand the mechanism of the cataract phenotype, we transgenically expressed different γD-crystallin mutants in the zebrafish lens and observed a range of lens defects that arise primarily from the aggregation of the mutant proteins. Unlike mouse models, a strong correlation was observed between the severity and penetrance of the phenotype and the level of destabilization of the mutant. We interpret this result to reflect the presence of a proteostasis network that can "sense" protein stability. In the more destabilized mutants, the capacity of this network is overwhelmed, leading to the observed increase in phenotypic penetrance. Overexpression of αA-crystallin had no significant effects on the penetrance of lens defects, suggesting that its chaperone capacity is not limiting. Although consistent with the prevailing hypothesis that a chaperone network is required for lens transparency, our results suggest that αA-crystallin may not be efficient to inhibit aggregation of lens γ-crystallin. Furthermore, our work implicates additional inputs/factors in this underlying proteostasis network and demonstrates the utility of zebrafish as a platform to delineate mechanisms of cataract.
[Mh] Termos MeSH primário: Catarata/genética
Cápsula do Cristalino/metabolismo
Mutação
Agregados Proteicos
Proteínas de Peixe-Zebra/biossíntese
Peixe-Zebra/metabolismo
gama-Cristalinas/biossíntese
[Mh] Termos MeSH secundário: Animais
Camundongos
Peixe-Zebra/genética
Proteínas de Peixe-Zebra/genética
Cadeia A de alfa-Cristalina/biossíntese
Cadeia A de alfa-Cristalina/genética
gama-Cristalinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Aggregates); 0 (Zebrafish Proteins); 0 (alpha-Crystallin A Chain); 0 (gamma-Crystallins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170526
[Lr] Data última revisão:
170526
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161023
[St] Status:MEDLINE


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[PMID]:26896727
[Au] Autor:Ghahramani M; Yousefi R; Khoshaman K; Moghadam SS; Kurganov BI
[Ad] Endereço:Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran.
[Ti] Título:Evaluation of structure, chaperone-like activity and protective ability of peroxynitrite modified human α-Crystallin subunits against copper-mediated ascorbic acid oxidation.
[So] Source:Int J Biol Macromol;87:208-21, 2016 Jun.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The copper-catalyzed oxidation of ascorbic acid (ASA) to dehydroascorbate (DHA) and hydrogen peroxide plays a central role in pathology of cataract diseases during ageing and in diabetic patients. In the current study, the structural feature, chaperone-like activity and protective ability of peroxynitrite (PON) modified αA- and αB-Crystallin (Cry) against copper-mediated ASA oxidation were studied using different spectroscopic measurements and gel mobility shift assay. Upon PON modification, additional to protein structural alteration, the contents of nitrotyrosine, nitrotryptophan, dityrosine and carbonyl groups were significantly increased. Moreover, αB-Cry demonstrates significantly larger capacity for PON modification than αA-Cry. Also, based on the extent of PON modification, these proteins may display an improved chaperone-like activity and enhanced protective ability against copper-mediated ASA oxidation. In the presence of copper ions, chaperone-like activity of both native and PON-modified α-Cry subunits were appreciably improved. Additionally, binding of copper ions to native and PON-modified proteins results in the significant reduction of their solvent exposed hydrophobic patches. Overall, the increase in chaperone-like activity/ASA protective ability of PON-modified α-Cry and additional enhancement of its chaperoning action with copper ions appear to be an important defense mechanism offered by this protein.
[Mh] Termos MeSH primário: Ácido Ascórbico/metabolismo
Cobre/metabolismo
Ácido Peroxinitroso/química
Cadeia A de alfa-Cristalina/química
Cadeia B de alfa-Cristalina/química
Cadeia B de alfa-Cristalina/metabolismo
[Mh] Termos MeSH secundário: Animais
Bovinos
Seres Humanos
Modelos Moleculares
Conformação de Ácido Nucleico
Cadeia A de alfa-Cristalina/genética
Cadeia A de alfa-Cristalina/metabolismo
Cadeia B de alfa-Cristalina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (alpha-Crystallin A Chain); 0 (alpha-Crystallin B Chain); 14691-52-2 (Peroxynitrous Acid); 789U1901C5 (Copper); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:161230
[Lr] Data última revisão:
161230
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160221
[St] Status:MEDLINE


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[PMID]:26700637
[Au] Autor:Takata T; Fujii N
[Ad] Endereço:Department of Biochemistry, Tokyo University of Pharmacy and Life Sciences, Japan.
[Ti] Título:Isomerization of Asp residues plays an important role in αA-crystallin dissociation.
[So] Source:FEBS J;283(5):850-9, 2016 Mar.
[Is] ISSN:1742-4658
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aged cataract formation is caused by the accumulative precipitation of lens proteins incorporating diverse post-translational modifications. α-Crystallin, a major structural and functional lens protein, consists of a large polymeric structure that is dissociated and insolubilized with accumulative post-translational modifications. One such modification, isomerization of Asp, was recently identified in αB-crystallin monomers derived from aged lens. However, the distributions of Asp isomers in each lens fraction remain unknown. Here, α-crystallin fractions from aged lens were separated into heteropolymeric and monomeric forms to determine the Asp isomerization ratios in each fraction. Lens of four different ages were homogenized and centrifuged, and the soluble fraction was applied to size-exclusion chromatography. The heteropolymeric α-crystallin and monomeric crystallin fractions were obtained and concentrated. After trypsin digestion, each fraction was independently applied to liquid chromatography equipped with mass spectrometry to extract α-crystallin-derived peptides containing Asp isomers. The results showed that Asp58, Asp84 and Asp151 of αA-crystallin were highly isomerized in the monomeric fraction, but not isomerized to the same level in the heteropolymeric fraction. Each type of Asp isomerization increased in an age-dependent manner, was site-specific and was similar to previous results from lens water-insoluble fractions. These results imply that isomerization of Asp residues leads to dissociation of αA-crystallin from the heteropolymeric state and induces insolubilization in aged lens. Taken together, our findings suggest that isomerization of Asp might disrupt the higher order polymeric state of α-crystallin, resulting in decreased solubility and function, ultimately contributing to lens protein impairment and cataract formation with aging.
[Mh] Termos MeSH primário: Envelhecimento
Ácido Aspártico/química
Cadeia A de alfa-Cristalina/química
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Catarata
Cromatografia
Cromatografia Líquida
Seres Humanos
Isomerismo
Cristalino/química
Meia-Idade
Polímeros/química
Ligação Proteica
Processamento de Proteína Pós-Traducional
Espectrometria de Massas em Tandem
Tripsina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Polymers); 0 (alpha-Crystallin A Chain); 30KYC7MIAI (Aspartic Acid); EC 3.4.21.4 (Trypsin)
[Em] Mês de entrada:1607
[Cu] Atualização por classe:160307
[Lr] Data última revisão:
160307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151225
[St] Status:MEDLINE
[do] DOI:10.1111/febs.13635



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