Yang Fan, Zhang Linxue, Gao Zhaopeng, Sun Xiaojiao, Yu Miao, Dong Shiyun, Wu Jichao, Zhao Yajun, Xu Changqing, Zhang Weihua, Lu Fanghao
Cell Physiol Biochem. 2017;43(3):1168-1187. doi: 10.1159/000481758. Epub 2017 Oct 5.
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.
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.
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.
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.
背景/目的：自噬通过细胞成分的处理和再循环在细胞稳态中发挥重要作用。硫化氢（H₂S）是第三种被证明具有心脏保护作用的内源性气体。鉴于自噬在心脏保护中的调节作用，本研究旨在探讨高糖处理期间硫化氢通过自噬产生的保护作用。
本研究检测了血浆以及心肌中H₂S的含量、线粒体和自噬体的超微结构变化。本研究还使用Hoechst/PI检测了凋亡率，以及在有或无GYY4137处理的H9C2细胞中自噬相关蛋白和线粒体凋亡蛋白的表达。分离了心脏组织的线粒体并检测了呼吸控制率（RCR）和ADP/O。用siRNA转染进行AMPK敲低。
在链脲佐菌素诱导的糖尿病模型中，NaHS处理不仅增加了糖尿病组中p-AMPK的表达，还进一步激活了细胞自噬。高糖处理48小时后，自噬体和细胞活力降低。目前的结果表明，H₂S可诱导自噬，这通过自噬超微结构观察和LC3-I/LC3-II转化得到验证。此外，线粒体膜电位（MMP）显著降低。自噬相关蛋白的表达水平显著升高。此外，H₂S激活了AMPK/雷帕霉素（mTOR）信号通路。
我们的研究结果表明，H₂S可降低氧化应激并防止线粒体损伤，激活自噬，并最终通过AMPK/mTOR途径实现心脏保护。
