Yanghui Wen1, Jun He1, Xiaofeng Xue1, Junyi Qiu1, Yinkai Xu1, Zuxiong Tang1, Haixin Qian1, Lei Qin1, Xiaohua Yang2. 1. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. 2. Department of General Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China. Electronic address: yangxiaohua@suda.edu.cn.
Abstract
BACKGROUND: Liver ischemia and reperfusion (I/R) is a common but severe clinical problem. Previous studies have revealed that the expression level of β-arrestin2 affects serum deprivation (SD)-induced cell apoptosis and was involved in lipopolysaccharide (LPS) stimulated TLR4 signaling pathway. However, little is known about β-arrestin2 in liver apoptosis and immune response induced by I/R. METHODS: A non-lethal model of segmental (70%) hepatic ischemia was utilized. Histology examination, cell apoptosis and cytokine levels were measured using H&E staining, TUNEL assay, and ELISA, respectively. Apoptosis-related protein and gene level of cytokines were respectively detected using Western blot and Real-time PCR. RESULTS: Our data showed that knockout (KO) of β-arrestin2 gene significantly deteriorated the injury of liver caused by I/R according to liver histology, higher serum liver enzyme, and increased level of cell apoptosis. β-arrestin2 KO could result in increased level of apoptosis related protein and decreased level of Akt phosphorylation. Furthermore, decreased levels of Bcl-2 and Bad phosphorylation, but increased level of Bax were found in β-arrestin2 KO group. In addition, the levels of p-ERK1/2, p-p38MAPKs, and p-NF-κB in β-arrestin2 KO group were significantly higher than that in WT group. CONCLUSIONS: β-arrestin2 protected liver from I/R injury and this effect may be due to the regulating of Akt pathway, Bcl-2/Bax ratio, MAPKs and NF-κB pathway.
BACKGROUND:Liver ischemia and reperfusion (I/R) is a common but severe clinical problem. Previous studies have revealed that the expression level of β-arrestin2 affects serum deprivation (SD)-induced cell apoptosis and was involved in lipopolysaccharide (LPS) stimulated TLR4 signaling pathway. However, little is known about β-arrestin2 in liver apoptosis and immune response induced by I/R. METHODS: A non-lethal model of segmental (70%) hepatic ischemia was utilized. Histology examination, cell apoptosis and cytokine levels were measured using H&E staining, TUNEL assay, and ELISA, respectively. Apoptosis-related protein and gene level of cytokines were respectively detected using Western blot and Real-time PCR. RESULTS: Our data showed that knockout (KO) of β-arrestin2 gene significantly deteriorated the injury of liver caused by I/R according to liver histology, higher serum liver enzyme, and increased level of cell apoptosis. β-arrestin2 KO could result in increased level of apoptosis related protein and decreased level of Akt phosphorylation. Furthermore, decreased levels of Bcl-2 and Bad phosphorylation, but increased level of Bax were found in β-arrestin2 KO group. In addition, the levels of p-ERK1/2, p-p38MAPKs, and p-NF-κB in β-arrestin2 KO group were significantly higher than that in WT group. CONCLUSIONS: β-arrestin2 protected liver from I/R injury and this effect may be due to the regulating of Akt pathway, Bcl-2/Bax ratio, MAPKs and NF-κB pathway.