Gaseous signal molecule SO₂ regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes

Abstract

Myocardial fibrosis is a key link in the occurrence and development of diabetic cardiomyopathy. Its etiology is complex, and the effect of drugs is not good. Cardiomyocyte apoptosis is an important cause of myocardial fibrosis. The purpose of this study was to investigate the effect of gaseous signal molecule sulfur dioxide (SO 2 ) on diabetic myocardial fibrosis and its internal regulatory mechanism. Masson and TUNEL staining, Western-blot, transmission electron microscopy, RT-qPCR, immunofluorescence staining, and flow cytometry were used in the study, and the interstitial collagen deposition, autophagy, apoptosis, and changes in phosphatidylinositol 3-kinase (PI3K)/AKT pathways were evaluated from in vivo and in vitro experiments. The results showed that diabetic myocardial fibrosis was accompanied by cardiomyocyte apoptosis and down-regulation of endogenous SO 2 -producing enzyme aspartate aminotransferase (AAT) 1/2 . However, exogenous SO 2 donors could up-regulate AAT 1/2 , reduce apoptosis of cardiomyocytes induced by diabetic rats or high glucose, inhibit phosphorylation of PI3K/AKT protein, up-regulate autophagy, and reduce interstitial collagen deposition. In conclusion, the results of this study suggest that the gaseous signal molecule SO 2 can inhibit the PI3K/AKT pathway to promote cytoprotective autophagy and inhibit cardiomyocyte apoptosis to improve myocardial fibrosis in diabetic rats. The results of this study are expected to provide new targets and intervention strategies for the prevention and treatment of diabetic cardiomyopathy.

Effects of gas signaling molecule SO2 in cardiac functions of hyperthyroid rats

“…Zhao et al . [ 60 ] also reported a decrease in endogenous SO 2 production in cardiomyocytes following high glucose stimulation. The results observed in this study suggested that administration of exogenous SO 2 donors significantly improved the myocardial fibrosis in hyperthyroid rats, restricted the ERS-activated, and inhibited apoptosis in cardiomyocytes.…”

Experimental model and novel therapeutic targets for non-alcoholic fatty liver disease development

“…Additionally, miR-34a decreases lipid absorption, lipogenesis, and autophagy by activating the sirtuin 1 (SIRT1)-mediated sterol regulatory element-binding transcription factor 1c (SREBP1c) signaling pathway ( Fig. 2B ) [ 52 , 53 ].…”

Salvianolic acid B ameliorates myocardial fibrosis in diabetic cardiomyopathy by deubiquitinating Smad7

“…Myocardial fibrosis is the primary pathological change in DCM [ 3 , 4 ]. The pathological features of myocardial fibrosis involve excess deposition of extracellular matrix (ECM) [ 5 ], resulting in the thickening and stiffness of the cardiac walls increased, leads to heart failure, cardiac dysfunction, arrhythmias, and heart attacks, and eventually cardiovascular death. [ 6 , 7 ].…”