| Texto completo | |
| Autor(es): |
Paviani, Veronica
[1]
;
de Melo, Paulo Junqueira
[2]
;
Avakin, Amaryllis
[2]
;
Di Mascio, Paolo
[1]
;
Ronsein, Graziella Eliza
[1]
;
Augusto, Ohara
[1]
Número total de Autores: 6
|
| Afiliação do(s) autor(es): | [1] Univ Sao Paulo, Inst Quim, Dept Bioquim, Av Lineu Prestes 748, BR-05508000 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Hosp Clin, Av Dr Eneas de Carvalho Aguiar 255, BR-05403000 Sao Paulo - Brazil
Número total de Afiliações: 2
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Free Radical Biology and Medicine; v. 160, p. 356-367, NOV 20 2020. |
| Citações Web of Science: | 0 |
| Resumo | |
Protein insolubilization, cross-linking and aggregation are considered critical to the development of lens opacity in cataract. However, the information about the presence of cross-links other than disulfides in cataractous lenses is limited. A potential role for cross-links produced from tryptophanyl radicals in cataract development is suggested by the abundance of the UV light-sensitive Trp residues in crystallin proteins. Here we developed a LCMS/MS approach to examine the presence of Trp-Trp, Trp-Tyr and Tyr-Tyr cross-links and of peptides containing Trp-2H (-2.0156 Da) in the lens of three patients diagnosed with advanced nuclear cataract. In the proteins of two of the lenses, we characterized intermolecular cross-links between beta B2-Tyr(153)-Tyr(104)-beta A3 and beta B2-Trp(150)-Tyr(139)-beta S. An additional intermolecular cross-link (beta B2-Tyr(61)-Trp(200)-beta B3) was present in the lens of the oldest patient. In the proteins of all three lenses, we characterized two intramolecular Trp-Trp cross-links (Trp(123)-Trp(126) in beta B1 and Trp(81)-Trp(84) in beta B2) and six peptides containing Trp -2H residues, which indicate the presence of additional Trp-Trp cross-links. Relevantly, we showed that similar cross-links and peptides with modified Trp-2H residues are produced in a time-dependent manner in bovine beta-crystallin irradiated with a solar simulator. Therefore, different crystallin proteins cross-linked by crystalline-derived tryptophanyl and tyrosyl radicals are present in advanced nuclear cataract lenses and similar protein modifications can be promoted by solar irradiation even in the absence of photosensitizers. Overall, the results indicate that a role for Trp-Tyr and Trp-Trp cross-links in the development of human cataract is possible and deserves further investigation. (AU) | |
| Processo FAPESP: | 16/00696-3 - Compreendendo composição e função da HDL através de proteômica |
| Beneficiário: | Graziella Eliza Ronsein |
| Modalidade de apoio: | Auxílio à Pesquisa - Jovens Pesquisadores |
| Processo FAPESP: | 13/07937-8 - Redoxoma |
| Beneficiário: | Ohara Augusto |
| Modalidade de apoio: | Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs |