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Hydrogen sulfide regulates SERCA2a SUMOylation by S-Sulfhydration of SENP1 to ameliorate cardiac systole-diastole function in diabetic cardiomyopathy.
- Source :
-
Biomedicine & Pharmacotherapy . Apr2023, Vol. 160, pN.PAG-N.PAG. 1p. - Publication Year :
- 2023
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Abstract
- Diabetic cardiomyopathy (DCM) is a serious complication of diabetes mellitus that eventually progresses to heart failure. The sarco(endo)plasmic reticulum calcium ATPase 2a (SERCA2a), an important calcium pump in cardiomyocytes, is closely related to myocardial systolic-diastolic function. In mammalian cells, hydrogen sulfide (H 2 S), as a second messenger, antioxidant, and sulfurizing agent, is involved in diverse biological processes. Despite the importance of H 2 S for protection against DCM, the mechanisms remain poorly understood. The aim of the present study was to determine whether H 2 S regulates intracellular calcium homeostasis by acting on SERCA2a to reduce cardiomyocyte apoptosis during DCM. Db/db mice were injected with NaHS for 18 weeks. Neonatal rat cardiomyocytes (NRCMs) were treated with high glucose, palmitate, oleate, and NaHS for 48 h. Compared to the NaHS-treated groups, in vivo and in vitro type 2 diabetic models both showed reduced intracellular H 2 S content, reduced cystathionine γ-lyase (CSE) expression, impaired cardiac function, decreased SERCA2a expression and decreased SERCA2a activity, reduced SUMOylation of SERCA2a, increased sentrin-specific protease 1 (SENP1) expression, and disruption of calcium homeostasis leading to activation of the mitochondrial apoptosis pathway. Compared to the NaHS-treated type 2 diabetes cellular model, overexpression of SENP1 C683A reduced the S-sulfhydration of SENP1, reduced the SUMOylation of SERCA2a, reduced the increased expression and activity of SERCA2a, and induced mitochondrial apoptosis in cardiomyocytes. These results suggested that exogenous H 2 S elevates SENP1 S-sulfhydration to increase SERCA2a SUMOylation, improve myocardial systolic-diastolic function, and decrease cardiomyocyte apoptosis in DCM. [Display omitted] • H 2 S content is reduced in diabetic cardiomyopathy. • Reduced the SUMOylation of SERCA2a in diabetic cardiomyopathy leads to decreased expression and activity of SERCA2a and imbalance in cellular calcium homeostasis. • H 2 S can S-sulfhydration the 683 cysteine site in the catalytic triad of SENP1. • Decreased S-sulfhydration of SENP1 Cys683 leads to decreased the SUMOylation of SERCA2a in diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 07533322
- Volume :
- 160
- Database :
- Academic Search Index
- Journal :
- Biomedicine & Pharmacotherapy
- Publication Type :
- Academic Journal
- Accession number :
- 162109819
- Full Text :
- https://doi.org/10.1016/j.biopha.2022.114200