antioxidants Article Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages Chaorui Guo, Inga Sileikaite, Michael J. Davies and Clare L. Hawkins * Department of Biomedical Sciences, University of Copenhagen, Panum, Blegdamsvej 3B, DK-2200 Copenhagen N, Denmark;
[email protected] (C.G.);
[email protected] (I.S.);
[email protected] (M.J.D.) * Correspondence:
[email protected]; Tel.: +45-35337005 Received: 29 September 2020; Accepted: 7 December 2020; Published: 10 December 2020 Abstract: 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−) 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−, to investigate the effects of generating a continuous flux of oxidants on macrophage cell function. Our studies show the generation of hydrogen peroxide (H2O2) 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−, 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.