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Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes

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 signa...

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Autores principales: Zhao, Junxiong, Wu, Qian, Yang, Ting, Nie, Liangui, Liu, Shengquan, Zhou, Jia, Chen, Jian, Jiang, Zhentao, Xiao, Ting, Yang, Jun, Chu, Chun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Korean Physiological Society and The Korean Society of Pharmacology 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614393/
https://www.ncbi.nlm.nih.gov/pubmed/36302628
http://dx.doi.org/10.4196/kjpp.2022.26.6.541
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author Zhao, Junxiong
Wu, Qian
Yang, Ting
Nie, Liangui
Liu, Shengquan
Zhou, Jia
Chen, Jian
Jiang, Zhentao
Xiao, Ting
Yang, Jun
Chu, Chun
author_facet Zhao, Junxiong
Wu, Qian
Yang, Ting
Nie, Liangui
Liu, Shengquan
Zhou, Jia
Chen, Jian
Jiang, Zhentao
Xiao, Ting
Yang, Jun
Chu, Chun
author_sort Zhao, Junxiong
collection PubMed
description 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.
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spelling pubmed-96143932022-11-04 Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes Zhao, Junxiong Wu, Qian Yang, Ting Nie, Liangui Liu, Shengquan Zhou, Jia Chen, Jian Jiang, Zhentao Xiao, Ting Yang, Jun Chu, Chun Korean J Physiol Pharmacol Original Article 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. The Korean Physiological Society and The Korean Society of Pharmacology 2022-11-01 2022-11-01 /pmc/articles/PMC9614393/ /pubmed/36302628 http://dx.doi.org/10.4196/kjpp.2022.26.6.541 Text en Copyright © Korean J Physiol Pharmacol https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/) ) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Article
Zhao, Junxiong
Wu, Qian
Yang, Ting
Nie, Liangui
Liu, Shengquan
Zhou, Jia
Chen, Jian
Jiang, Zhentao
Xiao, Ting
Yang, Jun
Chu, Chun
Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes
title Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes
title_full Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes
title_fullStr Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes
title_full_unstemmed Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes
title_short Gaseous signal molecule SO(2) regulates autophagy through PI3K/AKT pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type II diabetes
title_sort gaseous signal molecule so(2) regulates autophagy through pi3k/akt pathway inhibits cardiomyocyte apoptosis and improves myocardial fibrosis in rats with type ii diabetes
topic Original Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9614393/
https://www.ncbi.nlm.nih.gov/pubmed/36302628
http://dx.doi.org/10.4196/kjpp.2022.26.6.541
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