Exogenous H2S reduces the acetylation levels of mitochondrial respiratory enzymes via regulating the NAD( )-SIRT3 pathway in cardiac tissues of db/db mice
Exogenous H2S reduces the acetylation levels of mitochondrial respiratory enzymes via regulating the NAD( )-SIRT3 pathway in cardiac tissues of db/db mice
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外源 H2S 通过调节 db/db 小鼠心脏组织中的 NAD( )-SIRT3 通路降低线粒体呼吸酶的乙酰化水平
DOI：
10.1152/ajpendo.00326.2018
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Zhang Weihua
中科院分区：
文献类型：
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作者：
Sun Yu;Teng Zongyan;Sun Xiaojiao;Zhang Linxue;Chen Jian;Wang Bingzhu;Lu Fangping;Liu Ning;Yu Miao;Peng Shuo;Wang Yan;Zhao Dechao;Zhao Yajun;Ren Huan;Cheng Zhongyi;Dong Shiyun;Lu Fanghao;Zhang Weihua
硫化氢（H2S）是一种气体分子，参与调节多种生理功能，如抗氧化、抗高血压和多硫半胱氨酸的产生。H2S可能通过调节呼吸链酶活性抑制活性氧的产生和ATP的产生，但其作用机制尚不清楚。在这项研究中，db/db小鼠，新生大鼠心肌细胞，和H9c2细胞处理与高葡萄糖，油酸，棕榈酸被用作2型糖尿病的动物和细胞模型。与外源性H2S处理的indb/db小鼠相比，indb/db小鼠的线粒体呼吸速率、呼吸链复合体活性和ATP产生均降低。液相色谱-串联质谱分析表明，db/db小鼠心肌线粒体呼吸链相关蛋白乙酰化水平较NaHS处理组明显升高。外源性H2S可恢复高血糖和高血脂心肌细胞NAD +/NADH比值，增强sirtuin 3（SIRT3）的表达和活性，降低线粒体乙酰化水平。由于SIRT3的激活，呼吸抑制酶NADH脱氢酶1（ND1），泛醇细胞色素还原酶核心蛋白1和ATP合成酶线粒体F1复合物组装因子1的乙酰化减少，这增强了线粒体呼吸链活性和ATP产生的活性。我们得出结论，外源性H2S通过上调SIRT3在改善糖尿病患者心脏线粒体功能方面起着关键作用。
Hydrogen sulfide (H2S), a gaseous molecule, is involved in modulating multiple physiological functions, such as antioxidant, antihypertension, and the production of polysulfide cysteine. H2S may inhibit reactive oxygen species generation and ATP production through modulating respiratory chain enzyme activities; however, the mechanism of this effect remains unclear. In this study,db/dbmice, neonatal rat cardiomyocytes, and H9c2 cells treated with high glucose, oleate, and palmitate were used as animal and cellular models of type 2 diabetes. The mitochondrial respiratory rate, respiratory chain complex activities, and ATP production were decreased indb/dbmice compared with those indb/dbmice treated with exogenous H2S. Liquid chromatography with tandem mass spectrometry analysis showed that the acetylation level of proteins involved in the mitochondrial respiratory chain were increased in thedb/dbmice hearts compared with those with sodium hydrosulfide (NaHS) treatment. Exogenous H2S restored the ratio of NAD+/NADH, enhanced the expression and activity of sirtuin 3 (SIRT3) and decreased mitochondrial acetylation level in cardiomyocytes under hyperglycemia and hyperlipidemia. As a result of SIRT3 activation, acetylation of the respiratory complexe enzymes NADH dehydrogenase 1 (ND1), ubiquinol cytochromecreductase core protein 1, and ATP synthase mitochondrial F1 complex assembly factor 1 was reduced, which enhanced the activities of the mitochondrial respiratory chain activity and ATP production. We conclude that exogenous H2S plays a critical role in improving cardiac mitochondrial function in diabetes by upregulating SIRT3.