Kim, Hyo JeongJeong, Sun-OhJoe, YeonsooKong, Jin SunCho, Gyeong JaeRyter, Stefan W.Chung, Hun Taeg2014-03-112013Kim, Hyo Jeong, Yeonsoo Joe, Jin Sun Kong, Sun-Oh Jeong, Gyeong Jae Cho, Stefan W. Ryter, and Hun Taeg Chung. 2013. “Carbon Monoxide Protects against Hepatic Ischemia/Reperfusion Injury via ROS-Dependent Akt Signaling and Inhibition of Glycogen Synthase Kinase 3β.” Oxidative Medicine and Cellular Longevity 2013 (1): 306421. doi:10.1155/2013/306421. http://dx.doi.org/10.1155/2013/306421.1942-0900http://nrs.harvard.edu/urn-3:HUL.InstRepos:11879573Carbon 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.en-USJournal Article2014-03-1110.1155/2013/306421