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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2018-06-01
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| Series: | Redox Biology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S221323171830034X |
| _version_ | 1811309695965593600 |
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| author | Larissa A.C. Carvalho João P.P.B. Lopes Gilberto H. Kaihami Railmara P. Silva Alexandre Bruni-Cardoso Regina L. Baldini Flavia C. Meotti |
| author_facet | Larissa A.C. Carvalho João P.P.B. Lopes Gilberto H. Kaihami Railmara P. Silva Alexandre Bruni-Cardoso Regina L. Baldini Flavia C. Meotti |
| author_sort | Larissa A.C. Carvalho |
| collection | DOAJ |
| 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-/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. Keywords: Uric acid, Myeloperoxidase, Hypochlorous acid, dHL-60, Pseudomonas aeruginosa, Microbicidal |
| first_indexed | 2024-04-13T09:46:02Z |
| format | Article |
| id | doaj.art-bd2bd094576141caba1ad4577c078196 |
| institution | Directory Open Access Journal |
| issn | 2213-2317 |
| language | English |
| last_indexed | 2024-04-13T09:46:02Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Redox Biology |
| spelling | doaj.art-bd2bd094576141caba1ad4577c0781962022-12-22T02:51:46ZengElsevierRedox Biology2213-23172018-06-0116179188Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cellsLarissa A.C. Carvalho0João P.P.B. Lopes1Gilberto H. Kaihami2Railmara P. Silva3Alexandre Bruni-Cardoso4Regina L. Baldini5Flavia C. Meotti6Departamento de Bioquímica, Instituto de Química (IQUSP), Universidade de São Paulo, São Paulo, SP, BrazilDepartamento de Bioquímica, Instituto de Química (IQUSP), Universidade de São Paulo, São Paulo, SP, BrazilDepartamento de Bioquímica, Instituto de Química (IQUSP), Universidade de São Paulo, São Paulo, SP, BrazilDepartamento de Bioquímica, Instituto de Química (IQUSP), Universidade de São Paulo, São Paulo, SP, BrazilDepartamento de Bioquímica, Instituto de Química (IQUSP), Universidade de São Paulo, São Paulo, SP, BrazilDepartamento de Bioquímica, Instituto de Química (IQUSP), Universidade de São Paulo, São Paulo, SP, BrazilCorrespondence to: Instituto de Química (IQUSP), Universidade de São Paulo, Avenida Prof. Lineu Prestes, 748, bloco 10, sala 1001, CEP 05508-000 São Paulo, SP, Brazil.; Departamento de Bioquímica, Instituto de Química (IQUSP), Universidade de São Paulo, São Paulo, SP, BrazilUric 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-/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. Keywords: Uric acid, Myeloperoxidase, Hypochlorous acid, dHL-60, Pseudomonas aeruginosa, Microbicidalhttp://www.sciencedirect.com/science/article/pii/S221323171830034X |
| spellingShingle | Larissa A.C. Carvalho João P.P.B. Lopes Gilberto H. Kaihami Railmara P. Silva Alexandre Bruni-Cardoso Regina L. Baldini Flavia C. Meotti Uric acid disrupts hypochlorous acid production and the bactericidal activity of HL-60 cells Redox Biology |
| 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 |
| url | http://www.sciencedirect.com/science/article/pii/S221323171830034X |
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