Urate hydroperoxide oxidizes human peroxiredoxin 1 and peroxiredoxin 2

Autor(es)

Carvalho, Larissa A. C. ; Truzzi, Daniela R. ; Fallani, Thamiris S. ; Alves, Simone V. ; Toledo, Jose Carlos ; Augusto, Ohara ; Netto, Luis E. S. ; Meotti, Flavia C.

• Tipo de documento: Artigo Científico
• Fonte: Journal of Biological Chemistry; v. 292, n. 21, p. 8705-8715, MAY 26 2017.
• Citações Web of Science: 18

Resumo

Urate hydroperoxide is a product of the oxidation of uric acid by inflammatory heme peroxidases. The formation of urate hydroperoxide might be a key event in vascular inflammation, where there is large amount of uric acid and inflammatory peroxidases. Urate hydroperoxide oxidizes glutathione and sulfur-containing amino acids and is expected to react fast toward reactive thiols from peroxiredoxins (Prxs). The kinetics for the oxidation of the cytosolic 2-Cys Prx1 and Prx2 revealed that urate hydroperoxide oxidizes these enzymes at rates comparable with hydrogen peroxide. The second-order rate constants of these reactions were 4.9 x 10(5) and 2.3 x 10(6) m(-1) s(-1) for Prx1 and Prx2, respectively. Kinetic and simulation data suggest that the oxidation of Prx2 by urate hydroperoxide occurs by a three-step mechanism, where the peroxide reversibly associates with the enzyme; then it oxidizes the peroxidatic cysteine, and finally, the rate-limiting disulfide bond is formed. Of relevance, the disulfide bond formation was much slower in Prx2 (k(3) = 0.31 s(-1)) than Prx1 (k(3) = 14.9 s(-1)). In addition, Prx2 was more sensitive than Prx1 to hyperoxidation caused by both urate hydroperoxide and hydrogen peroxide. Urate hydroperoxide oxidized Prx2 from intact erythrocytes to the same extent as hydrogen peroxide. Therefore, Prx1 and Prx2 are likely targets of urate hydroperoxide in cells. Oxidation of Prxs by urate hydroperoxide might affect cell function and be partially responsible for the pro-oxidant and pro-inflammatory effects of uric acid. (AU)

• Processo FAPESP: 11/18106-4 - Oxidação do ácido úrico pela enzima mieloperoxidase em processos inflamatórios e as implicações sobre o sistema cardiovascular
• Beneficiário: Flavia Carla Meotti
• 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