H₂S-mediated blockage of protein acetylation and oxidative stress attenuates lipid overload-induced cardiac senescence

Abstract

Hydrogen sulphide (H₂S), a newly identified gasotransmitter, can be endogenously produced by cystathionine gamma-lyase (CSE) in the cardiovascular system. This study investigated the role of the CSE/H₂S system on lipid overload-induced lipotoxicity and cardiac senescence. Lipid overload in rat cardiomyocyte cells (H9C2) promoted intracellular accumulation of lipid, oxidative stress, mitochondrial dysfunctions, lipid peroxidation and inhibited cell viability, all of which could be reversed by exogenously applied H₂S. Further data revealed that H₂S protected H9C2 cells from lipid overload-induced senescence by altering the expressions of lipid metabolism-related genes and inhibiting cellular acetyl-CoA and global protein acetylation. Enhancement of protein acetylation abolished the protective role of H₂S on cardiac senescence. In vivo, knockout of the CSE gene strengthened cardiac lipid accumulation, protein acetylation, and cellular ageing in high fat diet-fed mice. Taken together, the CSE/H₂S system is capable of maintaining lipid homeostasis and cellular senescence in heart cells under lipid overload.

Keywords:

• H₂S
• cystathionine gamma-lyase
• lipotoxicity
• senescence
• protein acetylation

Disclosure statement

No competing financial interest exists.

Data availability statement

The data that support the findings of this study are available from the corresponding author, [GY], upon reasonable request.

Additional information

Funding

This study was supported by a discovery grant from the Natural Sciences and Engineering Research Council of Canada (RGPIN-2016–04051) and grand-in-aid from the Heart and Stroke Foundation of Canada (G-18–0022098).