Electrophiles modulate glutathione reductase activity via alkylation and upregulation of glutathione biosynthesis.

ABSTRACT: Cells evolved robust homeostatic mechanisms to protect against oxidation or alkylation by electrophilic species. Glutathione (GSH) is the most abundant intracellular thiol, protects cellular components from oxidation and is maintained in a reduced state by glutathione reductase (GR). Nitro oleic acid (NO₂-OA) is an electrophilic fatty acid formed under digestive and inflammatory conditions that both reacts with GSH and induces its synthesis upon activation of Nrf2 signaling. The effects of NO₂-OA on intracellular GSH homeostasis were evaluated. In addition to upregulation of GSH biosynthesis, we observed that NO₂-OA increased intracellular GSSG in an oxidative stress-independent manner. NO₂-OA directly inhibited GR in vitro by covalent modificati

SUBMITTER: Jobbagy S 

PROVIDER: S-EPMC6348771 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature