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Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells

Texto completo
Carvalho, Larissa A. C. [1] ; Lopes, Joao P. P. B. [1] ; Kaihami, Gilberto H. [1] ; Silva, Railmara P. [1] ; Bruni-Cardoso, Alexandre [1] ; Baldini, Regina L. [1] ; Meotti, Flavia C. [1]
Número total de Autores: 7
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Inst Quim IQUSP, Dept Bioquim, Sao Paulo, SP - Brazil
Número total de Afiliações: 1
Tipo de documento: Artigo Científico
Fonte: REDOX BIOLOGY; v. 16, p. 179-188, JUN 2018.
Citações Web of Science: 4

Uric acid is the end product of purine metabolism in humans and is an alternative physiological substrate for myeloperoxidase. Oxidation of uric acid by this enzyme generates uric acid free radical and urate hydroperoxide, a strong oxidant and potentially bactericide agent. In this study, we investigated whether the oxidation of uric acid and production of urate hydroperoxide would affect the killing activity of HL-60 cells differentiated into neutrophil-like cells (dHL-60) against a highly virulent strain (PA14) of the opportunistic pathogen Pseudomonas aeruginosa. While bacterial cell counts decrease due to dHL-60 killing, incubation with uric acid inhibits this activity, also decreasing the release of the inflammatory cytokines interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha). In a myeloperoxidase/Cl-/H2O2 cell-free system, uric acid inhibited the production of HOCl and bacterial killing. Fluorescence microscopy showed that uric acid also decreased the levels of HOCl produced by dHL-60 cells, while significantly increased superoxide production. Uric acid did not alter the overall oxidative status of dHL-60 cells as measured by the ratio of reduced (GSH) and oxidized (GSSG) glutathione. Our data show that uric acid impairs the killing activity of dHL-60 cells likely by competing with chloride by myeloperoxidase catalysis, decreasing HOCl production. Despite diminishing HOCl, uric acid probably stimulates the formation of other oxidants, maintaining the overall oxidative status of the cells. Altogether, our results demonstrated that HOCl is, indeed, the main relevant oxidant against bacteria and deviation of myeloperoxidase activity to produce other oxidants hampers dHL-60 killing activity. (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: 13/07937-8 - Redoxoma
Beneficiário:Ohara Augusto
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs