| Full text | |
| Author(s): |
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]
Total Authors: 7
|
| Affiliation: | [1] Univ Sao Paulo, Inst Quim IQUSP, Dept Bioquim, Sao Paulo, SP - Brazil
Total Affiliations: 1
|
| Document type: | Journal article |
| Source: | REDOX BIOLOGY; v. 16, p. 179-188, JUN 2018. |
| Web of Science Citations: | 4 |
| Abstract | |
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) | |
| FAPESP's process: | 11/18106-4 - Oxidation of uric acid by myeloperoxidase in inflammatory processes and the implications for cardiovascular disease |
| Grantee: | Flavia Carla Meotti |
| Support Opportunities: | Research Grants - Young Investigators Grants |
| FAPESP's process: | 13/07937-8 - Redoxome - Redox Processes in Biomedicine |
| Grantee: | Ohara Augusto |
| Support Opportunities: | Research Grants - Research, Innovation and Dissemination Centers - RIDC |