Base de dados : MEDLINE
Pesquisa : D12.776.306.366.300.100 [Categoria DeCS]
Referências encontradas : 80 [refinar]
Mostrando: 1 .. 10   no formato [Detalhado]

página 1 de 8 ir para página                    

  1 / 80 MEDLINE  
              next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28592682
[Au] Autor:Friedrich MG; Wang Z; Oakley AJ; Schey KL; Truscott RJW
[Ad] Endereço:Illawarra Health and Medical Research Institute, University of Wollongong, Wollongong, NSW 2500, Australia michaelf@uow.edu.au.
[Ti] Título:Hotspots of age-related protein degradation: the importance of neighboring residues for the formation of non-disulfide crosslinks derived from cysteine.
[So] Source:Biochem J;474(14):2475-2487, 2017 Jul 11.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo: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. Cys residues are another potential source of DHA, and evidence for this was found in many lens crystallins. In the human lens, some sites were more prone to forming non-disulfide covalent cross-links than others. Foremost among them was Cys5 in ßA4 crystallin. The reason for this enhanced reactivity was investigated using peptides. Oxidation of Cys to cystine was a prerequisite for DHA formation, and DHA production was accelerated markedly by the presence of a Lys, one residue separated from Cys5. Modeling and direct investigation of the N-terminal sequence of ßA4 crystallin, as well as a variety of homologous peptides, showed that the epsilon amino group of Lys can promote DHA production by nucleophilic attack on the alpha proton of cystine. Once a DHA residue was generated, it could form intermolecular cross-links with Lys and Cys. In the lens, the most abundant cross-link involved Cys5 of ßA4 crystallin attached via a thioether bond to glutathione. These findings illustrate the potential of Cys and disulfide bonds to act as precursors for irreversible covalent cross-links and the role of nearby amino acids in creating 'hotpsots' for the spontaneous processes responsible for protein degradation in aged tissues.
[Mh] Termos MeSH primário: Cisteína/química
Proteínas do Olho/química
Cristalino/química
[Mh] Termos MeSH secundário: Fatores Etários
Alanina/análogos & derivados
Alanina/química
Bases de Dados de Proteínas
Dissulfetos/química
Seres Humanos
Modelos Moleculares
Oligopeptídeos/química
Proteólise
Espectrometria de Massas em Tandem
Cadeia A de beta-Cristalina/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CRYBA4 protein, human); 0 (Disulfides); 0 (Eye Proteins); 0 (Oligopeptides); 0 (beta-Crystallin A Chain); 98RA387EKY (dehydroalanine); K848JZ4886 (Cysteine); OF5P57N2ZX (Alanine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171115
[Lr] Data última revisão:
171115
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170609
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20170268


  2 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28378818
[Au] Autor:Thomas MG; Maconachie G; Sheth V; McLean RJ; Gottlob I
[Ad] Endereço:Ulverscroft Eye Unit, Department of Neuroscience, Psychology and Behaviour, University of Leicester, Leicester, UK.
[Ti] Título:Development and clinical utility of a novel diagnostic nystagmus gene panel using targeted next-generation sequencing.
[So] Source:Eur J Hum Genet;25(6):725-734, 2017 Jun.
[Is] ISSN:1476-5438
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Infantile nystagmus (IN) is a genetically heterogeneous disorder arising from variants of genes expressed within the developing retina and brain. IN presents a diagnostic challenge and patients often undergo numerous investigations. We aimed to develop and assess the utility of a next-generation sequencing (NGS) panel to enhance the diagnosis of IN. We identified 336 genes associated with IN from the literature and OMIM. NimbleGen Human custom array was used to enrich the target genes and sequencing was performed using HiSeq2000. Using reference genome material (NA12878), we show the sensitivity (98.5%) and specificity (99.9%) of the panel. Fifteen patients with familial IN were sequenced using the panel. Two authors were masked to the clinical diagnosis. We identified variants in 12/15 patients in the following genes: FRMD7 (n=3), CACNA1F (n=2), TYR (n=5), CRYBA1 (n=1) and TYRP1 (n=1). In 9/12 patients, the clinical diagnosis was consistent with the genetic diagnosis. In 3/12 patients, the results from the genetic diagnoses (TYR, CRYBA1 and TYRP1 variants) enabled revision of clinical diagnoses. In 3/15 patients, we were unable to determine a genetic diagnosis. In one patient, copy number variation analysis revealed a FRMD7 deletion. This is the first study establishing the clinical utility of a diagnostic NGS panel for IN. We show that the panel has high sensitivity and specificity. The genetic information from the panel will lead to personalised diagnosis and management of IN and enable accurate genetic counselling. This will allow development of a new clinical care pathway for IN.
[Mh] Termos MeSH primário: Testes Genéticos/métodos
Nistagmo Congênito/genética
Análise de Sequência de DNA/métodos
[Mh] Termos MeSH secundário: Adolescente
Adulto
Canais de Cálcio Tipo L/genética
Criança
Pré-Escolar
Proteínas do Citoesqueleto/genética
Feminino
Testes Genéticos/normas
Seres Humanos
Masculino
Glicoproteínas de Membrana/genética
Proteínas de Membrana/genética
Nistagmo Congênito/diagnóstico
Oxirredutases/genética
Polimorfismo Genético
Sensibilidade e Especificidade
Análise de Sequência de DNA/normas
Cadeia A de beta-Cristalina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; VALIDATION STUDIES
[Nm] Nome de substância:
0 (CACNA1F protein, human); 0 (CRYBA1 protein, human); 0 (Calcium Channels, L-Type); 0 (Cytoskeletal Proteins); 0 (FRMD7 protein, human); 0 (Membrane Glycoproteins); 0 (Membrane Proteins); 0 (beta-Crystallin A Chain); EC 1.- (Oxidoreductases); EC 1.14.18.- (TYRP1 protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170406
[St] Status:MEDLINE
[do] DOI:10.1038/ejhg.2017.44


  3 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:28272538
[Au] Autor:Siggs OM; Javadiyan S; Sharma S; Souzeau E; Lower KM; Taranath DA; Black J; Pater J; Willoughby JG; Burdon KP; Craig JE
[Ad] Endereço:Department of Ophthalmology, Flinders University, Flinders Medical Centre, Bedford Park, South Australia, Australia.
[Ti] Título:Partial duplication of the CRYBB1-CRYBA4 locus is associated with autosomal dominant congenital cataract.
[So] Source:Eur J Hum Genet;25(6):711-718, 2017 Jun.
[Is] ISSN:1476-5438
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Congenital cataract is a rare but severe paediatric visual impediment, often caused by variants in one of several crystallin genes that produce the bulk of structural proteins in the lens. Here we describe a pedigree with autosomal dominant isolated congenital cataract and linkage to the crystallin gene cluster on chromosome 22. No rare single nucleotide variants or short indels were identified by exome sequencing, yet copy number variant analysis revealed a duplication spanning both CRYBB1 and CRYBA4. While the CRYBA4 duplication was complete, the CRYBB1 duplication was not, with the duplicated CRYBB1 product predicted to create a gain of function allele. This association suggests a new genetic mechanism for the development of isolated congenital cataract.
[Mh] Termos MeSH primário: Catarata/genética
Oftalmopatias Hereditárias/genética
Duplicação Gênica
Cadeia A de beta-Cristalina/genética
Cadeia B de beta-Cristalina/genética
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Catarata/patologia
Criança
Pré-Escolar
Cromossomos Humanos Par 22/genética
Variações do Número de Cópias de DNA
Oftalmopatias Hereditárias/patologia
Feminino
Seres Humanos
Masculino
Meia-Idade
Linhagem
Polimorfismo de Nucleotídeo Único
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CRYBA4 protein, human); 0 (CRYBB1 protein, human); 0 (beta-Crystallin A Chain); 0 (beta-Crystallin B Chain)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170309
[St] Status:MEDLINE
[do] DOI:10.1038/ejhg.2017.33


  4 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
[PMID]:28120589
[Au] Autor:Mohebi M; Akbari A; Babaei N; Sadeghi A; Heidari M
[Ad] Endereço:Farabi Eye Research Center, Farabi Eye Hospital, Tehran University of Medical Sciences, Tehran, Iran.
[Ti] Título:Identification of a De Novo 3bp Deletion in CRYBA1/A3 Gene in Autosomal Dominant Congenital Cataract.
[So] Source:Acta Med Iran;54(12):778-783, 2016 Dec.
[Is] ISSN:1735-9694
[Cp] País de publicação:Iran
[La] Idioma:eng
[Ab] Resumo:Autosomal dominant congenital cataract (ADCC) is the most common form of inherited cataracts and accounts for one-third of congenital cataracts. Heterozygous null mutations in the crystallin genes are the major cause of the ADCC. This study aims to detect the mutational spectrum of four crystallin genes, CRYBA1/A3, CRYBB1, CRYBB2 and CRYGD in an Iranian family. Genomic DNA was isolated from whole blood cells from theproband and other family members. The coding regions and flanking intronicsequences of crystalline genes were analyzed by Sanger sequencing in aproband with ADCC. The identified mutation was further evaluated in available family members. To predict the potential protein partners of CRYBA1/A3, we also used an in-silico analysis. A de novo heterozygous deletion (c.272-274delGAG, p.G91del) in exon 4 of CRYBA1/A3 gene, leading to a deletion of Glycine at codon 91 was found. This genetic variation did not change the reading frame of CRYBA1 protein. In conclusion, we identified a de novo in-frame 3-bp deletion in the proband with an autosomal dominant congenital cataract, but not in her parents, in an Iranian family. This mutation has occurred de novo on a paternal gamete during spermatogenesis. The in-silico results predicted the interaction of CRYBA1 protein with the other CRY as well as proteins responsible for eye cell signaling.
[Mh] Termos MeSH primário: Catarata/genética
Genes Dominantes/genética
Linhagem
Deleção de Sequência/genética
Cadeia A de beta-Cristalina/genética
[Mh] Termos MeSH secundário: Adulto
Grupo com Ancestrais do Continente Asiático/genética
Sequência de Bases
Catarata/sangue
Criança
Códon/genética
Análise Mutacional de DNA
Feminino
Variação Genética
Glicina/genética
Seres Humanos
Irã (Geográfico)
Masculino
Dados de Sequência Molecular
Mutação
Pais
Análise de Sequência de DNA/métodos
Cadeia A de beta-Cristalina/sangue
Cadeia B de beta-Cristalina/sangue
Cadeia B de beta-Cristalina/genética
gama-Cristalinas/sangue
gama-Cristalinas/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CRYBA1 protein, human); 0 (CRYBB1 protein, human); 0 (CRYGD protein, human); 0 (Codon); 0 (beta-Crystallin A Chain); 0 (beta-Crystallin B Chain); 0 (beta-crystallin B2); 0 (gamma-Crystallins); TE7660XO1C (Glycine)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170817
[Lr] Data última revisão:
170817
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170126
[St] Status:MEDLINE


  5 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:27208166
[Au] Autor:Leng XY; Li HY; Wang J; Qi LB; Xi YB; Yan YB
[Ad] Endereço:State Key Laboratory of Membrane Biology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
[Ti] Título:Congenital microcornea-cataract syndrome-causing mutation X253R increases ßB1-crystallin hydrophobicity to promote aggregate formation.
[So] Source:Biochem J;473(14):2087-96, 2016 Jul 15.
[Is] ISSN:1470-8728
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The high solubility and lifelong stability of crystallins are crucial to the maintenance of lens transparency and optical properties. Numerous crystallin mutations have been linked to congenital cataract, which is one of the leading causes of newborn blindness. Besides cataract, several crystallin mutations have also been linked to syndromes such as congenital microcornea-cataract syndrome (CMCC). However, the molecular mechanism of CMCC caused by crystallin mutations remains elusive. In the present study, we investigated the mechanism of CMCC caused by the X253R mutation in ßB1-crystallin. The exogenously expressed X253R proteins were prone to form p62-negative aggregates in HeLa cells, strongly inhibited cell proliferation and induced cell apoptosis. The intracellular X253R aggregates could be successfully redissolved by lanosterol but not cholesterol. The extra 26 residues at the C-terminus of ßB1-crystallin introduced by the X253R mutation had little impact on ßB1-crystallin structure and stability, but increased ßB1-crystallin hydrophobicity and decreased its solubility. Interestingly, the X253R mutant fully abolished the aggregatory propensity of ßB1- and ßA3/ßB1-crystallins at high temperatures, suggesting that X253R was an aggregation-inhibition mutation of ß-crystallin homomers and heteromers in dilute solutions. Our results suggest that an increase in hydrophobicity and a decrease in solubility might be responsible for cataractogenesis induced by the X253R mutation, while the cytotoxic effect of X253R aggregates might contribute to the defects in ocular development. Our results also highlight that, at least in some cases, the aggregatory propensity in dilute solutions could not fully mimic the behaviours of mutated proteins in the crowded cytoplasm of the cells.
[Mh] Termos MeSH primário: Catarata/genética
Catarata/metabolismo
Doenças da Córnea/genética
Doenças da Córnea/metabolismo
Agregação Patológica de Proteínas/metabolismo
Cadeia B de beta-Cristalina/química
Cadeia B de beta-Cristalina/metabolismo
[Mh] Termos MeSH secundário: Dicroísmo Circular
Células HeLa
Seres Humanos
Interações Hidrofóbicas e Hidrofílicas
Mutação/genética
Agregação Patológica de Proteínas/genética
Cadeia A de beta-Cristalina/química
Cadeia A de beta-Cristalina/genética
Cadeia A de beta-Cristalina/metabolismo
Cadeia B de beta-Cristalina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CRYBB1 protein, human); 0 (beta-Crystallin A Chain); 0 (beta-Crystallin B Chain)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170515
[Lr] Data última revisão:
170515
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160522
[St] Status:MEDLINE
[do] DOI:10.1042/BCJ20160247


  6 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:26022148
[Au] Autor:Zigler JS; Valapala M; Shang P; Hose S; Goldberg MF; Sinha D
[Ad] Endereço:Wilmer Eye Institute, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
[Ti] Título:ßA3/A1-crystallin and persistent fetal vasculature (PFV) disease of the eye.
[So] Source:Biochim Biophys Acta;1860(1 Pt B):287-98, 2016 Jan.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Persistent fetal vasculature (PFV) is a human disease in which the fetal vasculature of the eye fails to regress normally. The fetal, or hyaloid, vasculature nourishes the lens and retina during ocular development, subsequently regressing after formation of the retinal vessels. PFV causes serious congenital pathologies and is responsible for as much as 5% of blindness in the United States. SCOPE OF REVIEW: The causes of PFV are poorly understood, however there are a number of animal models in which aspects of the disease are present. One such model results from mutation or elimination of the gene (Cryba1) encoding ßA3/A1-crystallin. In this review we focus on the possible mechanisms whereby loss of functional ßA3/A1-crystallin might lead to PFV. MAJOR CONCLUSIONS: Cryba1 is abundantly expressed in the lens, but is also expressed in certain other ocular cells, including astrocytes. In animal models lacking ßA3/A1-crystallin, astrocyte numbers are increased and they migrate abnormally from the retina to ensheath the persistent hyaloid artery. Evidence is presented that the absence of functional ßA3/A1-crystallin causes failure of the normal acidification of endolysosomal compartments in the astrocytes, leading to impairment of certain critical signaling pathways, including mTOR and Notch/STAT3. GENERAL SIGNIFICANCE: The findings suggest that impaired endolysosomal signaling in ocular astrocytes can cause PFV disease, by adversely affecting the vascular remodeling processes essential to ocular development, including regression of the fetal vasculature. This article is part of a Special Issue entitled Crystallin Biochemistry in Health and Disease.
[Mh] Termos MeSH primário: Proteínas do Olho/metabolismo
Vítreo Primário Hiperplásico Persistente/embriologia
Vítreo Primário Hiperplásico Persistente/metabolismo
Vasos Retinianos/anormalidades
Vasos Retinianos/metabolismo
Cadeia A de beta-Cristalina/metabolismo
[Mh] Termos MeSH secundário: Animais
Doença Crônica
Seres Humanos
Modelos Biológicos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (CRYBA1 protein, human); 0 (Eye Proteins); 0 (beta-Crystallin A Chain)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:170101
[Lr] Data última revisão:
170101
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150530
[St] Status:MEDLINE


  7 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:26657544
[Au] Autor:Tiwary E; Hegde S; Purushotham S; Deivanayagam C; Srivastava O
[Ad] Endereço:Department of Vision Sciences, School of Optometry, University of Alabama at Birmingham, Birmingham, Alabama, 35294, United States of America.
[Ti] Título:Interaction of ßA3-Crystallin with Deamidated Mutants of αA- and αB-Crystallins.
[So] Source:PLoS One;10(12):e0144621, 2015.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Interaction among crystallins is required for the maintenance of lens transparency. Deamidation is one of the most common post-translational modifications in crystallins, which results in incorrect interaction and leads to aggregate formation. Various studies have established interaction among the α- and ß-crystallins. Here, we investigated the effects of the deamidation of αA- and αB-crystallins on their interaction with ßA3-crystallin using surface plasmon resonance (SPR) and fluorescence lifetime imaging microscopy-fluorescence resonance energy transfer (FLIM-FRET) methods. SPR analysis confirmed adherence of WT αA- and WT αB-crystallins and their deamidated mutants with ßA3-crystallin. The deamidated mutants of αA-crystallin (αA N101D and αA N123D) displayed lower adherence propensity for ßA3-crystallin relative to the binding affinity shown by WT αA-crystallin. Among αB-crystallin mutants, αB N78D displayed higher adherence propensity whereas αB N146D mutant showed slightly lower binding affinity for ßA3-crystallin relative to that shown by WT αB-crystallin. Under the in vivo condition (FLIM-FRET), both αA-deamidated mutants (αA N101D and αA N123D) exhibited strong interaction with ßA3-crystallin (32±4% and 36±4% FRET efficiencies, respectively) compared to WT αA-crystallin (18±4%). Similarly, the αB N78D and αB N146D mutants showed strong interaction (36±4% and 22±4% FRET efficiencies, respectively) with ßA3-crystallin compared to 18±4% FRET efficiency of WT αB-crystallin. Further, FLIM-FRET analysis of the C-terminal domain (CTE), N-terminal domain (NTD), and core domain (CD) of αA- and αB-crystallins with ßA3-crystallin suggested that interaction sites most likely reside in the αA CTE and αB NTD regions, respectively, as these domains showed the highest FRET efficiencies. Overall, results suggest that similar to WT αA- and WTαB-crystallins, the deamidated mutants showed strong interactionfor ßA3-crystallin. Variable in vitro and in vivo interactions are most likely due to the mutant's large size oligomers, reduced hydrophobicity, and altered structures. Together, the results suggest that deamidation of α-crystallin may facilitate greater interaction and the formation of large oligomers with other crystallins, and this may contribute to the cataractogenic mechanism.
[Mh] Termos MeSH primário: Amidas/metabolismo
Cristalinas/metabolismo
Processamento de Proteína Pós-Traducional
Cadeia B de alfa-Cristalina/metabolismo
Cadeia A de beta-Cristalina/metabolismo
[Mh] Termos MeSH secundário: Proteínas de Bactérias/genética
Proteínas de Bactérias/metabolismo
Sítios de Ligação
Cristalinas/química
Cristalinas/genética
Escherichia coli/genética
Escherichia coli/metabolismo
Expressão Gênica
Genes Reporter
Proteínas de Fluorescência Verde/genética
Proteínas de Fluorescência Verde/metabolismo
Células HeLa
Seres Humanos
Cristalino/química
Cristalino/metabolismo
Proteínas Luminescentes/genética
Proteínas Luminescentes/metabolismo
Mutagênese Sítio-Dirigida
Mutação
Ligação Proteica
Multimerização Proteica
Proteínas Recombinantes/química
Proteínas Recombinantes/genética
Proteínas Recombinantes/metabolismo
Transfecção
Cadeia B de alfa-Cristalina/química
Cadeia B de alfa-Cristalina/genética
Cadeia A de beta-Cristalina/química
Cadeia A de beta-Cristalina/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
0 (Amides); 0 (Bacterial Proteins); 0 (CRYAA protein, human); 0 (CRYAB protein, human); 0 (Crystallins); 0 (Cyan Fluorescent Protein); 0 (Luminescent Proteins); 0 (Recombinant Proteins); 0 (alpha-Crystallin B Chain); 0 (beta-Crystallin A Chain); 0 (yellow fluorescent protein, Bacteria); 147336-22-9 (Green Fluorescent Proteins)
[Em] Mês de entrada:1606
[Cu] Atualização por classe:161019
[Lr] Data última revisão:
161019
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151215
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0144621


  8 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25709017
[Au] Autor:Chebotareva NA; Eronina TB; Sluchanko NN; Kurganov BI
[Ad] Endereço:Bach Institute of Biochemistry, Russian Academy of Sciences, Leninsky pr. 33, Moscow 119071, Russia. Electronic address: chebotareva@inbi.ras.ru.
[Ti] Título:Effect of Ca2+ and Mg2+ ions on oligomeric state and chaperone-like activity of αB-crystallin in crowded media.
[So] Source:Int J Biol Macromol;76:86-93, 2015 May.
[Is] ISSN:1879-0003
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The main function of small heat shock proteins acting as suppressors of aggregation of non-native proteins is greatly influenced by crowded environment in the cell and the presence of divalent metal ions. The goal of the present work was to study the effects of Ca(2+) and Mg(2+) ions on the quaternary structure and anti-aggregation activity of αB-crystallin under crowding conditions. We showed that Ca(2+) and Mg(2+) ions induced formation of suboligomeric forms of αB-crystallin. This effect was retained in the presence of crowder (polyethylene glycol), although to a lesser degree. The chaperone-like activity of αB-crystallin was analyzed using heat-induced aggregation of myosin subfragment 1 (S1) at 40°C. In the absence of crowding agents chaperone-like activity of αB-crystallin exhibited low sensitivity to the presence of Ca(2+) and Mg(2+) ions. The addition of the crowding agents (polyethylene glycol 20000, Ficoll 70) dramatically increased S1 aggregation rates and significantly depressed anti-aggregation activity of αB-crystallin. Low concentrations of Ca(2+) (0.1mM) and Mg(2+) (10mM) partially restored the chaperone-like activity of αB-crystallin in the presence of crowders. This effect was observed at relatively low values of [αB-crystallin]/[S1] molar ratio, however, at [αB-crystallin]/[S1]>0.2 the stimulating effect of Ca(2+) became less pronounced. These findings might indicate that under crowded cell conditions different factors, including divalent cations, can effectively modulate chaperone-like activity of protein chaperones, which otherwise cannot properly cope with crowding-provoked accelerated rates of substrates aggregation.
[Mh] Termos MeSH primário: Cálcio/farmacologia
Íons/farmacologia
Magnésio/farmacologia
Multimerização Proteica/efeitos dos fármacos
Cadeia A de beta-Cristalina/química
Cadeia A de beta-Cristalina/metabolismo
[Mh] Termos MeSH secundário: Cálcio/química
Seres Humanos
Magnésio/química
Agregados Proteicos/efeitos dos fármacos
Ligação Proteica/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Ions); 0 (Protein Aggregates); 0 (beta-Crystallin A Chain); I38ZP9992A (Magnesium); SY7Q814VUP (Calcium)
[Em] Mês de entrada:1512
[Cu] Atualização por classe:150414
[Lr] Data última revisão:
150414
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150225
[St] Status:MEDLINE


  9 / 80 MEDLINE  
              first record previous record next record last record
seleciona
para imprimir
Fotocópia
PubMed Central Texto completo
Texto completo
[PMID]:25461968
[Au] Autor:Zigler JS; Sinha D
[Ad] Endereço:The Johns Hopkins University School of Medicine, The Wilmer Eye Institute, 400 North Broadway, Smith Building Room M037, Baltimore, MD 21231, USA. Electronic address: szigler1@jhmi.edu.
[Ti] Título:ßA3/A1-crystallin: more than a lens protein.
[So] Source:Prog Retin Eye Res;44:62-85, 2015 Jan.
[Is] ISSN:1873-1635
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Crystallins, the highly abundant proteins of the ocular lens, are essential determinants of the transparency and refractivity required for lens function. Initially thought to be lens-specific and to have evolved as lens proteins, it is now clear that crystallins were recruited to the lens from proteins that existed before lenses evolved. Crystallins are expressed outside of the lens and most have been shown to have cellular functions distinct from their roles as structural elements in the lens. For one major crystallin group, the ß/γ-crystallin superfamily, no such functions have yet been established. We have explored possible functions for the polypeptides (ßA3-and ßA1-crystallins) encoded by Cryba1, one of the 6 ß-crystallin genes, using a spontaneous rat mutant and genetically engineered mouse models. ßA3-and ßA1-crystallins are expressed in retinal astrocytes and retinal pigment epithelial (RPE) cells. In both cell types, these proteins appear to be required for the proper acidification of the lysosomes. In RPE cells, elevated pH in the lysosomes is shown to impair the critical processes of phagocytosis and autophagy, leading to accumulation of undigested cargo in (auto) phagolysosomes. We postulate that this accumulation may cause pathological changes in the cells resembling some of those characteristic of age-related macular degeneration (AMD). Our studies suggest an important regulatory function of ßA3/A1-crystallin in astrocytes. We provide evidence that the cellular function of ßA3/A1-crystallin involves its interaction with V-ATPase, the proton pump responsible for acidification of the endolysosomal system.
[Mh] Termos MeSH primário: Lisossomos/fisiologia
Retina/fisiologia
Cadeia A de beta-Cristalina/fisiologia
[Mh] Termos MeSH secundário: Animais
Astrócitos/metabolismo
Modelos Animais de Doenças
Seres Humanos
Camundongos
Ratos
Epitélio Pigmentado da Retina/metabolismo
Transdução de Sinais/fisiologia
ATPases Vacuolares Próton-Translocadoras/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, N.I.H., INTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; REVIEW
[Nm] Nome de substância:
0 (beta-Crystallin A Chain); EC 3.6.1.- (Vacuolar Proton-Translocating ATPases)
[Em] Mês de entrada:1507
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141203
[St] Status:MEDLINE


  10 / 80 MEDLINE  
              first record previous record
seleciona
para imprimir
Fotocópia
Texto completo
[PMID]:25450505
[Au] Autor:Sakaue H; Takata T; Fujii N; Sasaki H; Fujii N
[Ad] Endereço:Department of Chemistry, Graduate School of Science, Kyoto University, Sakyo-ku, Kyoto 606-8502, Japan.
[Ti] Título:Alpha B- and ßA3-crystallins containing d-aspartic acids exist in a monomeric state.
[So] Source:Biochim Biophys Acta;1854(1):1-9, 2015 Jan.
[Is] ISSN:0006-3002
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Crystallin stability and subunit-subunit interaction are essential for eye lens transparency. There are three types of crystallins in lens, designated as α-, ß-, and γ-crystallins. Alpha-crystallin is a hetero-polymer of about 800kDa, consisting of 35-40 subunits of two different αA- and αB-subunits, each of 20kDa. The ß/γ-crystallin superfamily comprises oligomeric ß-crystallin (2-6 subunits) and monomeric γ-crystallin. Since lens proteins have very long half-lives, they undergo numerous post-translational modifications including racemization, isomerization, deamidation, oxidation, glycation, and truncation, which may decrease crystallin solubility and ultimately cause cataract formation. Racemization and isomerization of aspartyl (Asp) residues have been detected only in polymeric α- and oligomeric ß-crystallin, while the situation in monomeric γ-crystallin has not been studied. Here, we investigated the racemization and isomerization of Asp in the γ-crystallin fraction of elderly donors. The results show that Asp residues of γS-, γD- and γC-crystallins were not racemized and isomerized. However, strikingly, we found that a portion of αB-crystallin and ßA3-crystallin moved to the lower molecular weight fraction which is the same size of γ-crystallin. In those fractions, Asp-96 of αB-crystallin and Asp-37 of ßA3-crystallin were highly inverted, which do not occur in the native lens higher molecular weight fraction. Our results indicate the possibility that the inversion of Asp residues may induce dissociation of αB- and ßA3-crystallins from the polymeric and oligomeric states. This is the first report that stereoinversion of amino acids disturbs lens protein assembly in aged human lens.
[Mh] Termos MeSH primário: Ácido D-Aspártico/química
Cristalino/química
Cadeia B de alfa-Cristalina/química
Cadeia A de beta-Cristalina/química
[Mh] Termos MeSH secundário: Idoso
Idoso de 80 Anos ou mais
Sequência de Aminoácidos
Catarata/metabolismo
Cromatografia Líquida de Alta Pressão
Cromatografia de Fase Reversa
Ácido D-Aspártico/metabolismo
Seres Humanos
Cristalino/metabolismo
Meia-Idade
Dados de Sequência Molecular
Fragmentos de Peptídeos/química
Fragmentos de Peptídeos/metabolismo
Solubilidade
Estereoisomerismo
Tripsina/metabolismo
Água/química
Cadeia B de alfa-Cristalina/metabolismo
Cadeia A de beta-Cristalina/metabolismo
gama-Cristalinas/química
gama-Cristalinas/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (CRYBA1 protein, human); 0 (Peptide Fragments); 0 (alpha-Crystallin B Chain); 0 (beta-Crystallin A Chain); 0 (gamma-Crystallins); 059QF0KO0R (Water); 4SR0Q8YD1X (D-Aspartic Acid); EC 3.4.21.4 (Trypsin)
[Em] Mês de entrada:1504
[Cu] Atualização por classe:161126
[Lr] Data última revisão:
161126
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:141203
[St] Status:MEDLINE



página 1 de 8 ir para página                    
   


Refinar a pesquisa
  Base de dados : MEDLINE Formulário avançado   

    Pesquisar no campo  
1  
2
3
 
           



Search engine: iAH v2.6 powered by WWWISIS

BIREME/OPAS/OMS - Centro Latino-Americano e do Caribe de Informação em Ciências da Saúde