Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages
Myeloperoxidase (MPO) is involved in the development of many chronic inflammatory diseases, in addition to its key role in innate immune defenses. This is attributed to the excessive production of hypochlorous acid (HOCl) by MPO at inflammatory sites, which causes tissue damage. This has sparked wid...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-12-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/9/12/1255 |
| _version_ | 1797545162328506368 |
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| author | Chaorui Guo Inga Sileikaite Michael J. Davies Clare L. Hawkins |
| author_facet | Chaorui Guo Inga Sileikaite Michael J. Davies Clare L. Hawkins |
| author_sort | Chaorui Guo |
| collection | DOAJ |
| description | Myeloperoxidase (MPO) is involved in the development of many chronic inflammatory diseases, in addition to its key role in innate immune defenses. This is attributed to the excessive production of hypochlorous acid (HOCl) by MPO at inflammatory sites, which causes tissue damage. This has sparked wide interest in the development of therapeutic approaches to prevent HOCl-induced cellular damage including supplementation with thiocyanate (SCN<sup>−</sup>) as an alternative substrate for MPO. In this study, we used an enzymatic system composed of glucose oxidase (GO), glucose, and MPO in the absence and presence of SCN<sup>−</sup>, to investigate the effects of generating a continuous flux of oxidants on macrophage cell function. Our studies show the generation of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) by glucose and GO results in a dose- and time-dependent decrease in metabolic activity and cell viability, and the activation of stress-related signaling pathways. Interestingly, these damaging effects were attenuated by the addition of MPO to form HOCl. Supplementation with SCN<sup>−</sup>, which favors the formation of hypothiocyanous acid, could reverse this effect. Addition of MPO also resulted in upregulation of the antioxidant gene, NAD(P)H:quinone acceptor oxidoreductase 1. This study provides new insights into the role of MPO in the modulation of macrophage function, which may be relevant to inflammatory pathologies. |
| first_indexed | 2024-03-10T14:11:34Z |
| format | Article |
| id | doaj.art-42ede9b760564d0fad588c9a8188a6e4 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T14:11:34Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-42ede9b760564d0fad588c9a8188a6e42023-11-21T00:08:51ZengMDPI AGAntioxidants2076-39212020-12-01912125510.3390/antiox9121255Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine MacrophagesChaorui Guo0Inga Sileikaite1Michael J. Davies2Clare L. Hawkins3Department of Biomedical Sciences, University of Copenhagen, Panum, Blegdamsvej 3B, DK-2200 Copenhagen N, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Panum, Blegdamsvej 3B, DK-2200 Copenhagen N, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Panum, Blegdamsvej 3B, DK-2200 Copenhagen N, DenmarkDepartment of Biomedical Sciences, University of Copenhagen, Panum, Blegdamsvej 3B, DK-2200 Copenhagen N, DenmarkMyeloperoxidase (MPO) is involved in the development of many chronic inflammatory diseases, in addition to its key role in innate immune defenses. This is attributed to the excessive production of hypochlorous acid (HOCl) by MPO at inflammatory sites, which causes tissue damage. This has sparked wide interest in the development of therapeutic approaches to prevent HOCl-induced cellular damage including supplementation with thiocyanate (SCN<sup>−</sup>) as an alternative substrate for MPO. In this study, we used an enzymatic system composed of glucose oxidase (GO), glucose, and MPO in the absence and presence of SCN<sup>−</sup>, to investigate the effects of generating a continuous flux of oxidants on macrophage cell function. Our studies show the generation of hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) by glucose and GO results in a dose- and time-dependent decrease in metabolic activity and cell viability, and the activation of stress-related signaling pathways. Interestingly, these damaging effects were attenuated by the addition of MPO to form HOCl. Supplementation with SCN<sup>−</sup>, which favors the formation of hypothiocyanous acid, could reverse this effect. Addition of MPO also resulted in upregulation of the antioxidant gene, NAD(P)H:quinone acceptor oxidoreductase 1. This study provides new insights into the role of MPO in the modulation of macrophage function, which may be relevant to inflammatory pathologies.https://www.mdpi.com/2076-3921/9/12/1255hypochlorous acidhypothiocyanous acidthiocyanateglucose oxidaseinflammationatherosclerosis |
| spellingShingle | Chaorui Guo Inga Sileikaite Michael J. Davies Clare L. Hawkins Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages Antioxidants hypochlorous acid hypothiocyanous acid thiocyanate glucose oxidase inflammation atherosclerosis |
| title | Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages |
| title_full | Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages |
| title_fullStr | Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages |
| title_full_unstemmed | Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages |
| title_short | Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages |
| title_sort | myeloperoxidase modulates hydrogen peroxide mediated cellular damage in murine macrophages |
| topic | hypochlorous acid hypothiocyanous acid thiocyanate glucose oxidase inflammation atherosclerosis |
| url | https://www.mdpi.com/2076-3921/9/12/1255 |
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