Lithium exacerbates hepatic ischemia/reperfusion injury by inhibiting GSK-3β/NF-κB-mediated protective signaling in mice.

Lithium (an inhibitor of GSK-3β activity) has beneficial effects on ischemia/reperfusion (I/R) injury in the central nervous system, heart and kidney. However, the role of lithium in hepatic I/R injury is unknown. The aim of this study was to assess the effects of lithium on hepatic I/R injury in a mouse model of partial hepatic I/R. Previous studies showed that lithium chloride (LiCl) can phosphorylate residue Ser9, inhibit GSK-3β activity, and improve I/R injury in other organs. In the present study, mice were pretreated with either vehicle or LiCl, which had similar effects on GSK-3β activity. Surprisingly, treatment with LiCl significantly exacerbated hepatic I/R injury, which was determined by serological and histological analyses. Acute and chronic LiCl treatment caused serious damage in hepatic I/R injury, including increased apoptosis and oxidative stress. To gain insight into the mechanism involved in this damage, the activity of nuclear factor-κB (NF-κB) (GSK-3β can regulate the transcriptional complex of NF-κB) was analyzed, which revealed that LiCl treatment significantly down-regulated the activity of NF-κB. The NF-κB-mediated protective genes were then further evaluated, including anti-apoptotic genes (RAF2, cIAP 2, Bfl-1 and cFLIP) and the antioxidant gene MnSOD. The expression of these protective genes was obviously suppressed compared with the vehicle group. Taken together, these findings show that lithium exacerbates hepatic I/R injury by suppressing the expression of GSK-3β/NF-κB-mediated protective genes.

Xia Y ，Rao J ，Yao A ，Zhang F ，Li G ，Wang X ，Lu L ... -  《-》

Inhibition of GSK-3beta ameliorates hepatic ischemia-reperfusion injury through GSK-3beta/beta-catenin signaling pathway in mice.

Xia YX ，Lu L ，Wu ZS ，Pu LY ，Sun BC ，Wang XH ... -  《Hepatobiliary & Pancreatic Diseases International》

Ionizing radiation can induce GSK-3beta phosphorylation and NF-kappaB transcriptional transactivation in ATM-deficient fibroblasts.

Kwon O ，Kim KA ，He L ，Kim SO ，Kim MS ，Cha EY ，Yoon BD ，Sok DE ，Jung M ，Ahn JS ，Kim BY ... -  《-》

Lithium chloride suppresses colorectal cancer cell survival and proliferation through ROS/GSK-3β/NF-κB signaling pathway.

Li H ，Huang K ，Liu X ，Liu J ，Lu X ，Tao K ，Wang G ，Wang J ... -  《-》

Diabetes Worsens Ischemia-Reperfusion Brain Injury in Rats Through GSK-3β.

Liu H ，Ou S ，Xiao X ，Zhu Y ，Zhou S ... -  《-》