Ischemic preconditioning increases GSK-3β/β-catenin levels and ameliorates liver ischemia/reperfusion injury in rats

Yan,Yichao; Li,Guangying; Tian,Xiaofeng; Ye,Yingjiang; Gao,Zhidong; Yao,Jihong; Zhang,Feng; Wang,Shan

doi:10.3892/ijmm.2015.2153

Ischemic preconditioning increases GSK-3β/β-catenin levels and ameliorates liver ischemia/reperfusion injury in rats

Authors:
- Yichao Yan
- Guangying Li
- Xiaofeng Tian
- Yingjiang Ye
- Zhidong Gao
- Jihong Yao
- Feng Zhang
- Shan Wang
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Affiliations: Department of Gastroenterological Surgery, Laboratory of Surgical Oncology, Peking University People's Hospital, Beijing 100044, P.R. China, Department of Gynaecology and Obstetrics, People's Liberation Army 202 Hospital, Shenyang, Liaoning 110002, P.R. China, Department of General Surgery, The Second Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116027, P.R. China, Department of Pharmacology, Dalian Medical University, Dalian, Liaoning 116044, P.R. China
Published online on: March 23, 2015 https://doi.org/10.3892/ijmm.2015.2153
Pages: 1625-1632

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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.

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