Hydrogen sulfide promoted retinoic acid-related orphan receptor α transcription to alleviate diabetic cardiomyopathy

Biochem Pharmacol. 2023 Aug 15:115748. doi: 10.1016/j.bcp.2023.115748. Online ahead of print.ABSTRACTDiabetic cardiomyopathy (DCM) is one serious and common complication in diabetes without effective treatments. Hydrogen sulfide (H2S) fights against a variety of cardiovascular diseases including DCM. Retinoic acid-related orphan receptor α (RORα) has protective effects on cardiovascular system. However, whether RORα mediates the protective effect of H2S against DCM remains unknown. The present research was to explore the roles and mechanisms of RORα in H2S against DCM. The study demonstrated that H2S donor sodium hydrosulfide (NaHS) alleviated cell injury but enhanced RORα expression in high glucose (HG)-stimulated cardiomyocytes. However, NaHS no longer had the protective effect on attenuating cell damage and oxidative stress, improving mitochondrial membrane potential, inhibiting necroptosis and enhanced signal transducer and activator of transcription 3 (STAT3) Ser727 phosphorylation in HG-stimulated cardiomyocytes after RORα siRNA transfection. Moreover, NaHS improved cardiac function, attenuated myocardial hypertrophy and fibrosis, alleviated oxidative stress, inhibited necroptosis, but increased STAT3 phosphorylation in wild type (WT) mice but not in RORα knockout mice (a spontaneous staggerer mice, sg/sg mice) with diabetes. Additionally, NaHS increased RORα promoter activity in cardiomyocytes with HG stimulation, which was related to the binding sites of E2F t...
Source: Biochemical Pharmacology - Category: Drugs & Pharmacology Authors: Source Type: research