Effects of inhibiting antioxidant pathways on cellular hydrogen sulfide and polysulfide metabolism

Free Radical Biology & Medicine
Kenneth R Olson, Yan Gao

Abstract

Elaborate antioxidant pathways have evolved to minimize the threat of excessive reactive oxygen species (ROS) and to regulate ROS as signaling entities. ROS are chemically and functionally similar to reactive sulfur species (RSS) and both ROS and RSS have been shown to be metabolized by the antioxidant enzymes, superoxide dismutase and catalase. Here we use fluorophores to examine the effects of a variety of inhibitors of antioxidant pathways on metabolism of two important RSS, hydrogen sulfide (H2S with AzMC) and polysulfides (H2Sn, where n = 2-7, with SSP4) in HEK293 cells. Cells were exposed to inhibitors for up to 5 days in normoxia (21% O2) and hypoxia (5% O2), conditions also known to affect ROS production. Decreasing intracellular glutathione (GSH) with l-buthionine-sulfoximine (BSO) or diethyl maleate (DEM) decreased H2S production for 5 days but did not affect H2Sn. The glutathione reductase inhibitor, auranofin, initially decreased H2S and H2Sn but after two days H2Sn increased over controls. Inhibition of peroxiredoxins with conoidin A decreased H2S and increased H2Sn, whereas the glutathione peroxidase inhibitor, tiopronin, increased H2S. Aminoadipic acid, an inhibitor of cystine uptake did not affect either H2S or ...Continue Reading

Citations

Feb 27, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Kenneth R OlsonKarl D Straubg
Aug 15, 2019·Antioxidants & Redox Signaling·Ling FuJing Yang
Feb 28, 2020·The Journal of Experimental Biology·Kenneth R Olson
Aug 24, 2019·Acta Physiologica·Kenneth R OlsonRobert V Stahelin
Jun 27, 2020·Antioxidants & Redox Signaling·Kenneth R Olson
Jul 8, 2020·International Journal of Molecular Sciences·Olivia Gross-AmatSerge Nataf
Jan 23, 2021·International Journal of Molecular Sciences·Kenneth R OlsonKarl D Straub

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