标题：Protective roles of hepatic gamma-aminobutyric acid signaling in acute ethanol exposure-induced liver injury
作者：Wang, Shuanglian; Sui, Shaofeng; Liu, Zhiyan; Peng, Cheng; Liu, Jia; Luo, Dan; Fan, Xinhuan; Liu, Chuanyong; Lu, Wei-Yang
作者机构：[Wang, Shuanglian; Luo, Dan; Fan, Xinhuan; Liu, Chuanyong] Shandong Univ, Sch Med, Dept Physiol, Jinan, Shandong, Peoples R China.; [Sui, Shaofeng] 更多
通讯作者：Liu, CY;Lu, WY
通讯作者地址：[Liu, CY]Shandong Univ, Sch Med, Dept Physiol, Jinan, Shandong, Peoples R China;[Lu, WY]Univ Western Ontario, Dept Physiol & Pharmacol, London, ON, Ca 更多
来源：JOURNAL OF APPLIED TOXICOLOGY
关键词：ERSR; ethanol; GABA(A)Rs; GAD; hepatocyte
摘要：Alcoholic liver disease (ALD) is a consequence of heavy and prolonged alcohol consumptions. We previously demonstrated a hepatic gamma-aminobutyric acid (GABA) signaling system that protects the liver from toxic injury. The present study was designed to investigate the role of the hepatic GABA signaling system in the process of acute ethanol exposure-induced liver injury. Our results showed that the expression of GABA synthesizing enzyme glutamic acid decarboxylase and type A GABA receptor (GABA(A)R) subunits was upregulated in ethanol-treated mice compared with saline-treated controls. Remarkably, pretreatment of mice with GABA (1.5 mg kg(-1) body weight, intraperitoneal injection [i.p.]) or with the GABA(A)R agonist muscimol (1.2 mg kg(-1) body weight, i.p.) protected the liver against ethanol toxicity and improved liver function, whereas pretreatment of mice with the GABA(A)R antagonist bicuculline (2.0 mg kg(-1) body weight, i.p.) worsened the liver function. Further analyses suggest that GABA(A)R-mediated signaling protects the liver from ethanol injury by, at least partially, inhibiting the IRE1 alpha-ASK1-JNK pro-apoptotic pathway in hepatocytes in the process of ethanol-induced endoplasmic reticulum stress response.