Busca avançada
Ano de início
Entree
(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Chemical Characterization of Urate Hydroperoxide, A Pro-oxidant Intermediate Generated by Urate Oxidation in Inflammatory and Photoinduced Processes

Texto completo
Autor(es):
Patricio, Eliziane S. [1] ; Prado, Fernanda M. [1] ; da Silva, Railmara P. [1] ; Carvalho, Larissa A. C. [1] ; Prates, Marcus V. C. [1] ; Dadamos, Tony [2] ; Bertotti, Mauro [2] ; Di Mascio, Paolo [1] ; Kettle, Anthony J. [3] ; Meotti, Flavia C. [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Dept Bioquim, Inst Quim, BR-05508000 Sao Paulo, SP - Brazil
[2] Univ Sao Paulo, Dept Quim, Inst Quim, BR-05508000 Sao Paulo, SP - Brazil
[3] Univ Otago, Dept Pathol, Ctr Free Radical Res, Christchurch 8140 - New Zealand
Número total de Afiliações: 3
Tipo de documento: Artigo Científico
Fonte: Chemical Research in Toxicology; v. 28, n. 8, p. 1556-1566, AUG 2015.
Citações Web of Science: 10
Resumo

Urate hydroperoxide is a strong oxidant generated by the combination of urate free radical and superoxide. The formation of urate hydroperoxide as an intermediate in urate oxidation is potentially responsible for the pro-oxidant effects of urate in inflammatory disorders, protein degradation, and food decomposition. To understand the molecular mechanisms that sustain the harmful effects of urate in inflammatory and oxidative stress related conditions, we report a detailed structural characterization and reactivity of urate hydroperoxide toward biomolecules. Urate hydroperoxide was synthesized by photo-oxidation and by a myeloperoxidase/hydrogen peroxide/superoxide system. Multiple reaction monitoring (MRM) and MS3 ion fragmentation revealed that urate hydroperoxide from both sources has the same chemical structure. Urate hydroperoxide has a maximum absorption at 308 nm, epsilon(308nm) = 6.54 +/- 0.38 x 10(3) M-1 cm(-1). This peroxide decays spontaneously with a rate constant of k = 2.80 +/- 0.18 x 10(-4) s(-1) and a half-life of 41 min at 22 degrees C. Urate hydropercodde undergoes electrochemical reduction at potential values less negative than -0.5 V (versus Ag/AgCl). When incubated with taurine, histidine, tryptophan, lysine, methionine, cysteine, or glutathione, urate hydroperwdde reacted only with methionine, cysteine, and glutathione. The oxidation of these molecules occurred by a two-electron mechanism, generating the alcohol, hydroxyisourate. No adduct between cysteine or glutathione and urate hydroperoxide was detected. The second-order rate constant for the oxidation of glutathione by urate hydroperoxide was 13.7 +/- 0.8 M-1 s(-1). In conclusion, the oxidation of sulfur-containing biomolecules by urate hydroperoxide is likely to be a mechanism by which the pro-oxidant and damaging effects of urate are mediated in inflammatory and photo-oxidizing processes. (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
Linha de fomento: Auxílio à Pesquisa - Apoio a Jovens Pesquisadores
Processo FAPESP: 11/15297-3 - Efeito do hidroperóxido de urato sobre a via da proteína dissulfeto isomerase e enzima NADPH oxidase (PDI-Nox) em processos inflamatórios do sistema cardiovascular
Beneficiário:Eliziane de Souza Patricio
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 13/02195-3 - Análise dos mecanismos pró-inflamatórios do hidroperóxido de urato sobre células do sistema imune inato: estudo sobre a via dos inflamassomas e proteínas moduladas por controle redox
Beneficiário:Larissa Anastacio da Costa Carvalho
Linha de fomento: Bolsas no Brasil - Doutorado