SIRT6 protects against hepatic ischemia/reperfusion injury by inhibiting apoptosis and autophagy related cell death
SIRT6 protects against hepatic ischemia/reperfusion injury by inhibiting apoptosis and autophagy related cell death
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SIRT6 通过抑制细胞凋亡和自噬相关的细胞死亡来防止肝缺血/再灌注损伤
DOI：
10.1016/j.freeradbiomed.2017.11.005
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发表时间：
2018-02
期刊：
影响因子：
--
通讯作者：
Yang Yang
中科院分区：
文献类型：
--
作者：
Song Zhang;Shuai Jiang;Haiping Wang;Wencheng Di;Chao Deng;Zhenxiao Jin;Wei Yi;Xiao Xiao;Yongzhan Nie;Yang Yang
沉默信息调节因子6(SIRT6)是一种组蛋白去乙酰基酶，参与肝脏的多种代谢过程，对多器官的缺血再灌注损伤具有重要的保护作用。在本研究中，我们探讨了SIRT6是否对肝脏I/R损伤具有保护作用，并阐明了其可能的机制。再灌注期SIRT6的表达较对照组明显降低。与对照小鼠相比，SIRT6-LKO小鼠的氧化应激、线粒体功能障碍、炎症反应、丝裂原活化蛋白激酶(MAPK)信号的激活以及与肝细胞凋亡和自噬相关的死亡显著加重。相反，SIRT6上调可减轻肝I/R损伤所致的肝损伤。我们的研究首次证明SIRT6上调对肝脏I/R损伤有有效的保护作用。其潜在的机制包括维持氧化稳态和线粒体功能，从而抑制炎症反应和MAPK信号转导，最终减轻肝细胞凋亡和自噬相关的死亡。提示SIRT6的激活对肝脏I/R损伤具有多方面的保护作用，可为肝脏I/R损伤提供新的治疗靶点。
Silent information regulator 6 (SIRT6), a class III histone deacetylase, has been revealed to participate in multiple metabolic processes in the liver, and it plays important roles in protecting against ischemia/reperfusion (I/R) injury in multiple organs. In this study, we explored whether SIRT6 is protective against hepatic I/R injury and elucidated the underlying mechanisms. The expression of SIRT6 was significantly decreased during reperfusion compared with the control group. SIRT6-LKO mice exhibited significantly aggravated oxidative stress, mitochondrial dysfunction, inflammatory responses, mitogen-activated protein kinase (MAPK) signaling activation, and apoptosis and autophagy related hepatocyte death compared with control mice.In vitrostudies in SIRT6-KO hepatocytes exhibited similar results. In contrast, SIRT6 upregulation alleviated liver damage during hepatic I/R injury. Our study demonstrated for the first time that SIRT6 upregulation effectively protects against hepatic I/R injury. The underlying mechanisms involve the maintenance of oxidative homeostasis and mitochondrial function, which subsequently inhibit the inflammatory responses and MAPK signaling, and finally attenuate apoptosis and autophagy related hepatocyte death. These results suggest that the activation of SIRT6 exerts multifaceted protective effects during hepatic I/R injury, which can provide a novel therapeutic target for hepatic I/R injury.
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DOI：
10.1007/s00534-009-0155-x
发表时间：
2009-11-01
期刊：
JOURNAL OF HEPATO-BILIARY-PANCREATIC SURGERY
影响因子：
--
作者：
King, LaShonda A.;Toledo, Alexander H.;Toledo-Pereyra, Luis H.
通讯作者：
Toledo-Pereyra, Luis H.
姜黄素预处理激活 SIRT1 可减轻心肌缺血再灌注损伤引起的线粒体氧化损伤
影响因子：
7.4
作者：
Yang, Yang;Duan, Weixun;Jin, Zhenxiao
通讯作者：
Jin, Zhenxiao
影响因子：
8
作者：
Becatti, Matteo;Taddei, Niccolo;Fiorillo, Claudia
通讯作者：
Fiorillo, Claudia
影响因子：
4.6
作者：
He, Song-Qing;Zhang, Yan-Hong;Wu, Jian
通讯作者：
Wu, Jian
影响因子：
9.5
作者：
Wang, Xiao-Xiao;Wang, Xu-Lei;Jiang, Wei
通讯作者：
Jiang, Wei