Protective role of silent information regulator 1 against hepatic ischemia: effects on oxidative stress injury, inflammatory response, and MAPKs
Protective role of silent information regulator 1 against hepatic ischemia: effects on oxidative stress injury, inflammatory response, and MAPKs
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沉默信息调节因子1对肝缺血的保护作用：对氧化应激损伤、炎症反应和MAPK的影响
DOI：
10.1517/14728222.2016.1153067
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发表时间：
2016-03
影响因子：
5.8
通讯作者：
Jin Zhenxiao
中科院分区：
文献类型：
--
作者：
Yang Yang;Zhang Song;Fan Chongxi;Yi Wei;Jiang Shuai;Di Shouyi;Ma Zhiqiang;Hu Wei;Deng Chao;Lv Jianjun;Li Tian;Nie Yongzhan;Jin Zhenxiao
摘要目的：沉默信息调节因子1（SIRT 1）是一种III类组蛋白去乙酰化酶，对缺血再灌注损伤具有保护作用。在这项研究中，我们研究了SIRT 1是否可以保护肝脏IRI，并探讨了潜在的机制。研究设计和方法：我们使用肝特异性SIRT 1 −/-小鼠、SIRT 1 siRNA转染的肝细胞和SIRT 1 +/+肝细胞在体内和体外检测SIRT 1是否可以保护肝脏IRI。结果：与对照组相比，再灌注期间SIRT 1的表达和活性明显降低。与对照小鼠相比，肝脏特异性SIRT 1 −/-小鼠表现出肝损伤标志物的显著增加以及氧化应激和炎症反应的增加。体外研究显示了类似的结果。此外，SIRT 1上调通过p-JNK、p-p38 MAPK和p-ERK的过表达来保护肝脏IRI。SIRT 1的保护作用可被p38 MAPK、JNK和ERK抑制剂有效逆转。结论：SIRT 1的激活可显著抑制肝脏IRI时的氧化应激和炎症反应，有望成为肝脏IRI的一种新的保护机制。
ABSTRACT Objective: Previous studies have verified that silent information regulator 1 (SIRT1), a class III histone deacetylase, protects against ischemia reperfusion (IR) injury (IRI) in some organs. In this study, we examined whether SIRT1 could protect against hepatic IRI and explored the potential mechanisms. Research design and methods: We examined whether SIRT1 could protect against hepatic IRI in vivo and in vitro using hepatic-specific SIRT1−/- mice, SIRT1 siRNA-transfected hepatocytes and SIRT1+/+ hepatocytes. Results: The expression and activity of SIRT1 were significantly reduced during reperfusion compared with that observed in the control group. Hepatic-specific SIRT1−/- mice exhibited significant increase of hepatic damage markers and augment of oxidative stress and inflammatory response compared with control mice. In vitro studies demonstrated similar results. Furthermore, SIRT1 upregulation protects against hepatic IRI, through the overexpression of p-JNK, p-p38MAPK, and p-ERK. The protection of SIRT1 can be effectively reversed by the inhibitors of p38MAPK, JNK, and ERK. Conclusion: The activation of SIRT1 significantly inhibits the oxidative stress and inflammatory response during hepatic IRI, which can be developed as a novel method to protect against hepatic IRI.
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脂多糖预处理通过抑制小鼠 ATF4-CHOP 通路来保护肝细胞免受缺血/再灌注损伤 (IRI)。
影响因子：
3.7
作者：
Rao J;Qin J;Qian X;Lu L;Wang P;Wu Z;Zhai Y;Zhang F;Li G;Wang X
通讯作者：
Wang X
影响因子：
9.8
作者：
Bordone L;Motta MC;Picard F;Robinson A;Jhala US;Apfeld J;McDonagh T;Lemieux M;McBurney M;Szilvasi A;Easlon EJ;Lin SJ;Guarente L
通讯作者：
Guarente L
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：
3.9
作者：
Harada, H;Hines, IN;Grisham, MB
通讯作者：
Grisham, MB