DHRS7 Integrates NADP⁺/NADPH Redox Sensing with Inflammatory Lipid Signalling via the Oxoeicosanoid Pathway.

ABSTRACT: During the innate immune response at epithelial wound sites, oxidative stress acts microbicidal and-mechanistically less well understood-as an immune and resilience signal. The reversible sulfhydryl (SH) oxidation of kinases, phosphatases, and transcription factors constitute the perhaps best-known redox signalling paradigm, whereas mechanisms that transduce metabolic redox cues, such as redox cofactor balance, remain little explored. Here, using mammalian cells, microsomes, and live zebrafish, we identify DHRS7, a short-chain fatty acid dehydrogenase/reductase (SDR), as conserved, 5-hydroxyeicosanoid dehydrogenase (5-HEDH). Under oxidative stress, DHRS7 consumes NADP⁺ to convert arachidonic acid (AA)-derived 5(S)-HETE into the inflammatory lipid 5-KETE, which activates leukocyt

SUBMITTER: Ma Y 

PROVIDER: S-EPMC11839141 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature