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Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells
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 investi...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952876/ https://www.ncbi.nlm.nih.gov/pubmed/29510342 http://dx.doi.org/10.1016/j.redox.2018.02.020 |
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author | Carvalho, Larissa A.C. Lopes, João P.P.B. Kaihami, Gilberto H. Silva, Railmara P. Bruni-Cardoso, Alexandre Baldini, Regina L. Meotti, Flavia C. |
author_facet | Carvalho, Larissa A.C. Lopes, João P.P.B. Kaihami, Gilberto H. Silva, Railmara P. Bruni-Cardoso, Alexandre Baldini, Regina L. Meotti, Flavia C. |
author_sort | Carvalho, Larissa A.C. |
collection | PubMed |
description | 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-1β (IL-1β) and tumor necrosis factor-α (TNF- α). In a myeloperoxidase/Cl(-)/H(2)O(2) 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. |
format | Online Article Text |
id | pubmed-5952876 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-59528762018-05-16 Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells Carvalho, Larissa A.C. Lopes, João P.P.B. Kaihami, Gilberto H. Silva, Railmara P. Bruni-Cardoso, Alexandre Baldini, Regina L. Meotti, Flavia C. Redox Biol Research Paper 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-1β (IL-1β) and tumor necrosis factor-α (TNF- α). In a myeloperoxidase/Cl(-)/H(2)O(2) 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. Elsevier 2018-03-01 /pmc/articles/PMC5952876/ /pubmed/29510342 http://dx.doi.org/10.1016/j.redox.2018.02.020 Text en © 2018 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Research Paper Carvalho, Larissa A.C. Lopes, João P.P.B. Kaihami, Gilberto H. Silva, Railmara P. Bruni-Cardoso, Alexandre Baldini, Regina L. Meotti, Flavia C. Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells |
title | Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells |
title_full | Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells |
title_fullStr | Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells |
title_full_unstemmed | Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells |
title_short | Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells |
title_sort | uric acid disrupts hypochlorous acid production and the bactericidal activity of hl-60 cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5952876/ https://www.ncbi.nlm.nih.gov/pubmed/29510342 http://dx.doi.org/10.1016/j.redox.2018.02.020 |
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