β-Arrestin 2 Promotes Hepatocyte Apoptosis by Inhibiting Akt Pathway in Alcoholic Liver Disease.
β-Arrestin 2 Promotes Hepatocyte Apoptosis by Inhibiting Akt Pathway in Alcoholic Liver Disease.
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DOI：
10.3389/fphar.2018.01031
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发表时间：
2018
影响因子：
5.6
通讯作者：
Li J
中科院分区：
文献类型：
--
作者：
Sun YY;Zhao YX;Li XF;Huang C;Meng XM;Li J
酒精性肝病（ALD）是一个复杂的过程，包括广泛的肝脏病变，从脂肪变性到肝硬化，甚至肝细胞癌（HCC）。越来越多的证据表明，酒精代谢的细胞毒性作用导致细胞凋亡和坏死。近年来，多功能蛋白β-arrestin 2（Arrb 2）在肝纤维化和肝癌中调控细胞凋亡，但其在ALD中的作用尚不完全清楚。本研究旨在探讨Arrb 2在ALD肝细胞存活和凋亡中的作用及其机制。在我们的研究中，原代肝细胞分离自C57 BL/6小鼠的肝脏喂养含乙醇的饮食，它显示了Arrb 2的水平增加。EtOH还在体外显着上调AML-12细胞中Arrb 2的产生。TUNEL（末端脱氧核苷酸转移酶介导的dUTP缺口末端标记）和流式细胞术（FCM）结果表明，敲低Arrb 2可抑制乙醇诱导的肝细胞凋亡，而过表达Arrb 2可诱导ALD细胞凋亡。Western blot结果显示Arrb 2显著抑制Akt信号通路。综上所述，我们的数据表明，Arrb 2可能作为一个潜在的治疗ALD的目标，通过促进肝细胞凋亡Akt抑制。
Alcoholic liver disease (ALD) is a complex process that includes a wide range of hepatic lesions, from steatosis to cirrhosis, and even hepatocellular carcinoma (HCC). Accumulating evidence shows that the cytotoxic effects of ethanol metabolism lead to cell apoptosis and necrosis in ALD. Recently, several studies revealed that multifunctional protein β-arrestin 2 (Arrb2) modulated cell apoptosis in liver fibrosis and HCC, but its role in ALD has not been fully understood. The aim of this study is to explore the function and underlying mechanism of Arrb2 in hepatocyte survival and apoptosis in ALD. In our study, the primary hepatocytes were isolated from the livers of C57BL/6 mice fed EtOH-containing diet, it showed an increased level of Arrb2. EtOH also significantly up-regulated Arrb2 production in AML-12 cells in vitro. Furthermore, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) and FCM results demonstrated that knockdown of Arrb2 could inhibit hepatocyte apoptosis induced by EtOH in vivo and vitro while over-expression of Arrb2 induced apoptosis in ALD. In addition, western blot results revealed that Arrb2 remarkably suppressed the Akt signaling. Taken together, our data suggested that Arrb2 may serve as a potential therapeutic target for ALD by promoting hepatocyte apoptosis via Akt suppression.
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