Exogenous hydrogen sulfide inhibits apoptosis by regulating endoplasmic reticulum stress–autophagy axis and improves myocardial reconstruction after acute myocardial infarction. (19th November 2020)

• Record Type: Journal Article
• Authors: Li, Yaling; Liu, Maojun; Yi, Jiali; Song, Xiong; Zheng, Xia; Liu, Da; Wang, Sen; Chu, Chun; Yang, Jun
• Is Part Of: Acta biochimica et biophysica Sinica. Volume 52:Number 12(2020)
• Page Start: 1325
• Page End: 1336
• Publication Date: 2020-11-19
• Subjects: hydrogen sulfide -- myocardial reconstruction -- endoplasmic reticulum stress–autophagy axis -- apoptosis -- acute myocardial infarction; Biochemistry -- Periodicals; Biophysics -- Periodicals; 572.05
• DOI: 10.1093/abbs/gmaa133
• Languages: English
• ISSNs: 1672-9145

Abstract

Abstract: During acute myocardial infarction, endoplasmic reticulum (ER) stress-induced autophagy and apoptosis have been shown as important pathogeneses of myocardial reconstruction. Importantly, hydrogen sulfide (H2 S), as a third endogenous gas signaling molecule, exerts strong cytoprotective effect on anti-ER stress, autophagy regulation and antiapoptosis. Here, we showed that H2 S treatment inhibits apoptosis by regulating ER stress–autophagy axis and improves myocardial reconstruction after acute myocardial infarction. We found that H2 S intervention improved left ventricle function, reduced glycogen deposition in myocardial tissue mesenchyme, and inhibited apoptosis. Moreover, the expressions of fibrosis indicators (Col3a1 and Col1a2), ER stress-related proteins (CHOP and BIP/ERP78), autophagy-related proteins (Beclin and ATG5), apoptosis protein (Bax), as well as fibrosis protein Col4a3bp were all decreased after treatment with H2 S. H2 S administration also maintained MMP/TIMP balance. Mechanistically, H2 S activated the PI3K/AKT signaling pathway. In addition, H2 S treatment also reduced the expressions of ER stress–related proteins, autophagy-related proteins, and apoptins in in vitro experiments. Interestingly, activation of ER stress–autophagy axis could reverse the inhibitory effect of H2 S on myocardial apoptosis. Altogether, these results suggested that exogenous H2 S suppresses myocardial apoptosis by blocking ER stress–autophagy axis, which in turn reverses cardiac remodeling after myocardial infarction.