Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages
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Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages. / Guo, Chaorui; Sileikaite, Inga; Davies, Michael J.; Hawkins, Clare L.
I: Antioxidants, Bind 9, Nr. 12, 1255, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Myeloperoxidase Modulates Hydrogen Peroxide Mediated Cellular Damage in Murine Macrophages
AU - Guo, Chaorui
AU - Sileikaite, Inga
AU - Davies, Michael J.
AU - Hawkins, Clare L.
PY - 2020
Y1 - 2020
N2 - 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. This study provides new insights into the role of MPO in the modulation of macrophage function, which may be relevant to inflammatory pathologies.
AB - 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. This study provides new insights into the role of MPO in the modulation of macrophage function, which may be relevant to inflammatory pathologies.
KW - hypochlorous acid
KW - hypothiocyanous acid
KW - thiocyanate
KW - glucose oxidase
KW - inflammation
KW - atherosclerosis
KW - macrophage
KW - HYPOCHLOROUS ACID
KW - HYPOTHIOCYANOUS ACID
KW - COMPARATIVE REACTIVITY
KW - CYSTIC-FIBROSIS
KW - THIOCYANATE
KW - OXIDANTS
KW - STRESS
KW - CELLS
KW - ACTIVATION
KW - MECHANISMS
U2 - 10.3390/antiox9121255
DO - 10.3390/antiox9121255
M3 - Journal article
C2 - 33321763
VL - 9
JO - Antioxidants
JF - Antioxidants
SN - 2076-3921
IS - 12
M1 - 1255
ER -
ID: 256934774