title: Ischemic preconditioning increases GSK-3β/β-catenin levels and ameliorates liver ischemia/reperfusion injury in rats.
abstract: Ischemic preconditioning (IPC) ameliorates ischemia/reperfusion (I/R) injury in a number of organs, and the glycogen synthase kinase-3β (GSK-3β)/β-catenin signaling pathway regulates I/R-induced proliferation and apoptosis in the central nervous system and heart. However, the function of this signaling pathway in IPC during liver I/R remains unclear. Thus, in this study, we aimed to investigte the role of the GSK-3β/β-catenin pathway during I/R and following ischemic preconditioning. For this purpose, 30 Sprague-Dawley rats were randomly divided into the sham-operated, the I/R and the IPC groups (n=10). Following reperfusion, liver pathology, as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), maleic dialdehyde (MDA) and superoxide dismutase (SOD) levels were assessed. Western blot analysis was performed to quantify the GSK-3β, Ser9-phospho-GSK-3β (p-GSK-3β), cytosolic and nuclear β-catenin, vascular endothelial growth factor (VEGF), Bcl-2 and survivin levels. In addition, the Bcl-2 and survivin mRNA levels were assessed by RT-qPCR. Compared with the sham-operated group, I/R increased serum ALT, AST and MDA activity and decreased SOD levels, while IPC significantly decreased serum ALT, AST and MDA activity and increased SOD levels, compared with the I/R group. Simultaneously, I/R increased p-GSK-3β protein expression, and decreased Bcl-2 and survivin protein and mRNA levels. IPC further increased the protein expression of p-GSK-3β, and also increased cytosolic and nuclear β-catenin and VEGF expression compared with the I/R group; the expression of Bcl-2 and survivin was also increased by IPC, both at the mRNA and protein level. The total GSK-3β expression remained unaltered in all the groups. In conclusion, our data demonstrate that IPC exerts protective effects against liver injury induced by I/R and activates the GSK-3β/β-catenin signaling pathway.
authors: Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors: Yichao
authors: Y
authors: Yan
authors: Department of Gynaecology and Obstetrics, People's Liberation Army 202 Hospital, Shenyang, Liaoning 110002, P.R. China.
authors: Guangying
authors: G
authors: Li
authors: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors: Xiaofeng
authors: X
authors: Tian
authors: Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors: Yingjiang
authors: Y
authors: Ye
authors: Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors: Zhidong
authors: Z
authors: Gao
authors: Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China.
authors: Jihong
authors: J
authors: Yao
authors: Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China.
authors: Feng
authors: F
authors: Zhang
authors: Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, P.R. China.
authors: Shan
authors: S
authors: Wang
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D000071679:Glycogen Synthase Kinase 3 beta; D019194:Ischemic Preconditioning; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism* / Q000473:pathology / Q000517:prevention & control*; D015398:Signal Transduction; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3