Cystathione β-synthase regulates HIF-1α stability through persulfidation of PHD2.

ABSTRACT: The stringent expression of the hypoxia inducible factor-1α (HIF-1α) is critical to a variety of pathophysiological conditions. We reveal that, in normoxia, enzymatic action of cystathionine β-synthase (CBS) produces H₂S, which persulfidates prolyl hydroxylase 2 (PHD2) at residues Cys²¹ and Cys³³ (zinc finger motif), augmenting prolyl hydroxylase activity. Depleting endogenous H₂S either by hypoxia or by inhibiting CBS via chemical or genetic means reduces persulfidation of PHD2 and inhibits activity, preventing hydroxylation of HIF-1α, resulting in stabilization. Our in vitro findings are further supported by the depletion of CBS in the zebrafish model that exhibits axis defects and abnormal intersegmental vessels. Exogenous H₂S suppl

SUBMITTER: Dey A 

PROVIDER: S-EPMC7458453 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature