Hypoxic preconditioning protects against ischemic kidney injury through the IDO1/kynurenine pathway.

ABSTRACT: Prolonged cellular hypoxia leads to energetic failure and death. However, sublethal hypoxia can trigger an adaptive response called hypoxic preconditioning. While prolyl-hydroxylase (PHD) enzymes and hypoxia-inducible factors (HIFs) have been identified as key elements of oxygen-sensing machinery, the mechanisms by which hypoxic preconditioning protects against insults remain unclear. Here, we perform serum metabolomic profiling to assess alterations induced by two potent cytoprotective approaches, hypoxic preconditioning and pharmacologic PHD inhibition. We discover that both approaches increase serum kynurenine levels and enhance kynurenine biotransformation, leading to preservation of NAD⁺ in the post-ischemic kidney. Furthermore, we show that indoleamine 2,3-dioxygenase 1 (I

SUBMITTER: Torosyan R 

PROVIDER: S-EPMC8487442 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature