Exogenous H2S Protects Against Diabetic Cardiomyopathy by Activating Autophagy via the AMPK/mTOR Pathway.
Fan Yang,Linxue Zhang,Zhaopeng Gao,Xiaojiao Sun,Miao Yu,Shiyun Dong,Jichao Wu,Yajun Zhao,Changqing Xu,Weihua Zhang,Fanghao Lu +10 more
TLDR
The findings demonstrated that H2S decreases oxidative stress and protects against mitochondria injury, activates autophagy, and eventually leads to cardiac protection via the AMPK/mTOR pathway.Abstract:
Background/aim Autophagy plays an important role in cellular homeostasis through the disposal and recycling of cellular components. Hydrogen sulphide (H2S) is the third endogenous gas that has been shown to confer cardiac protective effects. Given the regulation of autophagy in cardioprotection, this study aimed to investigate the protective effects of H2S via autophagy during high glucose treatment. Methods This study investigated the content of H2S in the plasma as well as myocardial, ultrastructural changes in mitochondria and autophagosomes. This study also investigated the apoptotic rate using Hoechst/PI as well as expression of autophagy-associated proteins and mitochondrial apoptotic proteins in H9C2 cells treated with or without GYY4137. Mitochondria of cardiac tissues were isolated and RCR and ADP/O were also detected. AMPK knockdown was performed with siRNA transfection. Results In a STZ-induced diabetic model, NaHS treatment not only increased the expression of p-AMPK in diabetic group but further activated cell autophagy. Following 48h high glucose, autophagosomes and cell viability were reduced. The present results showed that autophagy could be induced by H2S, which was verified by autophagic ultrastructural observation and LC3-I/LC3-II conversion. In addition, the mitochondrial membrane potential (MMP) was significantly decreased. The expressions levels of autophagic-related proteins were significantly elevated. Moreover, H2S activated the AMPK/rapamycin (mTOR) signalling pathway. Conclusions Our findings demonstrated that H2S decreases oxidative stress and protects against mitochondria injury, activates autophagy, and eventually leads to cardiac protection via the AMPK/mTOR pathway.read more
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TL;DR: In vitro, ALP increased Nrf2 and reduced the hyperglycaemia‐induced increases of H9C2 cardiomyocyte hypertrophy, oxidative stress, apoptosis and autophagy, and enhanced cellular viability, while in vivo ALP reverted all the above‐mentioned diabetes‐induced biochemical changes.
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Saikat Dewanjee,Jayalakshmi Vallamkondu,Rajkumar Singh Kalra,Albin John,P. Hemachandra Reddy,Ramesh Kandimalla +5 more
TL;DR: In this article, the role of autophagy and its adaptations in the diabetic heart was assessed and the potential pharmacotherapeutic strategies towards targeting autophagia were discussed.
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