A thiol redox sensor in soluble epoxide hydrolase enables oxidative activation by intra-protein disulfide bond formation.

ABSTRACT: Soluble epoxide hydrolase (sEH), an enzyme that broadly regulates the cardiovascular system, hydrolyses epoxyeicosatrienoic acids (EETs) to their corresponding dihydroxyeicosatrienoic acids (DHETs). We previously showed that endogenous lipid electrophiles adduct within the catalytic domain, inhibiting sEH to lower blood pressure in angiotensin II-induced hypertensive mice. As angiotensin II increases vascular H₂O₂, we explored sEH redox regulation by this oxidant and how this integrates with inhibition by lipid electrophiles to regulate vasotone. Kinetics analyses revealed that H₂O₂ not only increased the specific activity of sEH but increased its affinity for substrate and increased its catalytic efficiency. This oxidative activation was mediate

SUBMITTER: Charles RL 

PROVIDER: S-EPMC8436062 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature