| First Author | Zhang S | Year | 2023 |
| Journal | Biochem Pharmacol | Volume | 215 |
| Pages | 115748 | PubMed ID | 37591449 |
| Mgi Jnum | J:340643 | Mgi Id | MGI:7524937 |
| Doi | 10.1016/j.bcp.2023.115748 | Citation | Zhang S, et al. (2023) Hydrogen sulfide promoted retinoic acid-related orphan receptor alpha transcription to alleviate diabetic cardiomyopathy. Biochem Pharmacol 215:115748 |
| abstractText | Diabetic cardiomyopathy (DCM) is one serious and common complication in diabetes without effective treatments. Hydrogen sulfide (H(2)S) fights against a variety of cardiovascular diseases including DCM. Retinoic acid-related orphan receptor alpha (RORalpha) has protective effects on cardiovascular system. However, whether RORalpha mediates the protective effect of H(2)S against DCM remains unknown. The present research was to explore the roles and mechanisms of RORalpha in H(2)S against DCM. The study demonstrated that H(2)S donor sodium hydrosulfide (NaHS) alleviated cell injury but enhanced RORalpha 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 RORalpha 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 RORalpha knockout mice (a spontaneous staggerer mice, sg/sg mice) with diabetes. Additionally, NaHS increased RORalpha promoter activity in cardiomyocytes with HG stimulation, which was related to the binding sites of E2F transcription factor 1 (E2F1) in the upstream region of RORalpha promoter. NaHS enhanced E2F1 expression and increased the binding of E2F1 to RORalpha promoter in cardiomyocytes with HG stimulation. In sum, H(2)S promoted RORalpha transcription via E2F1 to alleviate necroptosis and protect against DCM. It is helpful to propose a novel therapeutic implication for DCM. |
