Carbon monoxide protects against hepatic ischemia/reperfusion injury via ROS-dependent Akt signaling and inhibition of glycogen synthase kinase 3β.
Carbon monoxide protects against hepatic ischemia/reperfusion injury via ROS-dependent Akt signaling and inhibition of glycogen synthase kinase 3β.
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DOI：
10.1155/2013/306421
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发表时间：
2013
影响因子：
--
通讯作者：
Chung HT
中科院分区：
文献类型：
--
作者：
Kim HJ;Joe Y;Kong JS;Jeong SO;Cho GJ;Ryter SW;Chung HT
一氧化碳（CO）可通过调节细胞信号通路在生理和病理生理状态中发挥重要作用。CO通过调节细胞内氧化还原状态、抑制炎症反应、凋亡反应和增殖反应，保护器官组织免受缺血/再灌注（I/R）损伤。然而，CO在器官I/R损伤中保护作用的细胞机制仍不完全清楚。在这项研究中，小鼠模型的肝脏热I/R损伤的糖原合成酶激酶-3（GSK 3）和磷脂酰肌醇3-激酶（PI 3 K）依赖的信号通路的作用进行评估的保护作用的CO对炎症和损伤。通过PI 3 K/Akt途径抑制GSK 3在CO介导的保护中起关键作用。CO处理增加了I/R损伤后肝脏Akt和GSK 3-β（GSK 3 β）的磷酸化。此外，PI 3 K抑制剂LY 294002可降低CO的保护作用，并降低I/R损伤后磷酸化GSK 3 β的水平。这些结果表明，CO通过维持GSK 3 β磷酸化来保护肝损伤，这可能是通过PI 3 K/Akt信号通路介导的。我们的研究为CO在器官损伤中的治疗潜力提供了额外的支持，并确定GSK 3 β作为CO改善肝损伤的治疗靶点。
Carbon monoxide (CO) may exert important roles in physiological and pathophysiological states through the regulation of cellular signaling pathways. CO can protect organ tissues from ischemia/reperfusion (I/R) injury by modulating intracellular redox status and by inhibiting inflammatory, apoptotic, and proliferative responses. However, the cellular mechanisms underlying the protective effects of CO in organ I/R injury remain incompletely understood. In this study, a murine model of hepatic warm I/R injury was employed to assess the role of glycogen synthase kinase-3 (GSK3) and phosphatidylinositol 3-kinase (PI3K)-dependent signaling pathways in the protective effects of CO against inflammation and injury. Inhibition of GSK3 through the PI3K/Akt pathway played a crucial role in CO-mediated protection. CO treatment increased the phosphorylation of Akt and GSK3-beta (GSK3β) in the liver after I/R injury. Furthermore, administration of LY294002, an inhibitor of PI3K, compromised the protective effect of CO and decreased the level of phospho-GSK3β after I/R injury. These results suggest that CO protects against liver damage by maintaining GSK3β phosphorylation, which may be mediated by the PI3K/Akt signaling pathway. Our study provides additional support for the therapeutic potential of CO in organ injury and identifies GSK3β as a therapeutic target for CO in the amelioration of hepatic injury.
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DOI：
10.4049/jimmunol.1101323
发表时间：
2012-06-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Deng J;Wang X;Qian F;Vogel S;Xiao L;Ranjan R;Park H;Karpurapu M;Ye RD;Park GY;Christman JW
通讯作者：
Christman JW
影响因子：
4.4
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通讯作者：
Michalek, SM
影响因子：
10.8
作者：
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Li, Chuanfu
影响因子：
4.6
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Murase, Noriko
DOI：
10.1152/ajpgi.00144.2007
发表时间：
2008-01-01
影响因子：
4.5
作者：
Kaizu, Takashi;Ikeda, Atsushi;Murase, Noriko
通讯作者：
Murase, Noriko