当前位置: X-MOL 学术Acta Biochim. Biophys. Sin. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Exogenous hydrogen sulfide inhibits apoptosis by regulating endoplasmic reticulum stress–autophagy axis and improves myocardial reconstruction after acute myocardial infarction
Acta Biochimica et Biophysica Sinica ( IF 3.3 ) Pub Date : 2020-11-19 , DOI: 10.1093/abbs/gmaa133
Yaling Li 1 , Maojun Liu 1 , Jiali Yi 1 , Xiong Song 1 , Xia Zheng 1 , Da Liu 1 , Sen Wang 1 , Chun Chu 2 , Jun Yang 1
Affiliation  

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 (H2S), as a third endogenous gas signaling molecule, exerts strong cytoprotective effect on anti-ER stress, autophagy regulation and antiapoptosis. Here, we showed that H2S treatment inhibits apoptosis by regulating ER stress–autophagy axis and improves myocardial reconstruction after acute myocardial infarction. We found that H2S 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 H2S. H2S administration also maintained MMP/TIMP balance. Mechanistically, H2S activated the PI3K/AKT signaling pathway. In addition, H2S 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 H2S on myocardial apoptosis. Altogether, these results suggested that exogenous H2S suppresses myocardial apoptosis by blocking ER stress–autophagy axis, which in turn reverses cardiac remodeling after myocardial infarction.


中文翻译:

外源性硫化氢通过调节内质网应激-自噬轴抑制细胞凋亡,并改善急性心肌梗死后的心肌重建

摘要
在急性心肌梗塞期间,内质网(ER)应激诱导的自噬和细胞凋亡已显示为心肌重建的重要病原体。重要的是,硫化氢(H 2 S)作为第三种内源性气体信号分子,对抗ER应激,自噬调节和抗凋亡具有强大的细胞保护作用。在这里,我们证明了H 2 S治疗通过调节ER应力-自噬轴抑制细胞凋亡,并改善了急性心肌梗塞后的心肌重建。我们发现H 2S干预改善了左心室功能,减少了心肌组织间充质中糖原的沉积,并抑制了细胞凋亡。此外,纤维化指标(Col3a1和Col1a2),ER应激相关蛋白(CHOP和BIP / ERP78),自噬相关蛋白(Beclin和ATG5),凋亡蛋白(Bax)以及纤维化蛋白Col4a3bp的表达都用H处理后降低2 S.H。2行政体系也保持MMP / TIMP平衡。从机理上讲,H 2 S激活了PI3K / AKT信号通路。此外,在体外,H 2 S处理还降低了ER应激相关蛋白,自噬相关蛋白和凋亡素的表达实验。有趣的是,内质网应激自噬轴的激活可以逆转H 2 S对心肌细胞凋亡的抑制作用。总而言之,这些结果表明,外源性H 2 S通过阻断ER应力-自噬轴来抑制心肌细胞凋亡,从而逆转心肌梗塞后的心脏重塑。
更新日期:2020-12-29
down
wechat
bug