Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

ABSTRACT: The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands. This covalent inactivation slows entry of proteins into the Cys/N-degron pathway that ADO initiates. HYZ's capacity to stabilize regulators of G-protein signaling (RGS4/5) normally marked for degradation by ADO explains its effect on blood vessel tension and comports with prior associations of insufficient RGS levels

SUBMITTER: Shishikura K 

PROVIDER: S-EPMC11722266 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature