Relationship between oxidative stress and hepatic glutathione levels in ethanol-mediated apoptosis of polarized hepatic cells

作     者：Benita L McVicker Pamela L Tuma Kusum K Kharbanda Serene ML Lee Dean J Tuma 

作者机构：Liver Study UnitDepartment of Veterans Affairs Medical Center and Department of Internal Medicine and Biochemistry & Molecular BiologyUniversity of Nebraska Medical Center Department of BiologyThe Catholic University of America Department of Internal Medicine and Biochemistry & Molecular BiologyUniversity of Nebraska Medical Center 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2009年第15卷第21期

页      面：2609-2616页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by The National Institute on Alcohol Abuse and Alcoholism and by the Department of Veterans Affairs 

主　　题：WIF-B cells Alcohol Fas/CD95 Glutathi-one Caspase 

摘      要：AIM： To investigate the role of reactive oxygen species （ROS） in ethanol-mediated cell death of polarized hepatic （WlF-B） cells. METHODS： In this work, WIF-B cultures were treated with pyrazole （inducer of cytochrome P4502E1, CYP2E1） and/or L-buthionine sulfoximine （BSO）, a known inhibitor of hepatic glutathione （GSH）, followed by evaluation of ROS production, antioxidant levels, and measures of cell injury （apoptosis and necrosis）. RESULTS： The results revealed that ethanol treatment alone caused a significant two-fold increase in the activation of caspase-3 as well as a similar doubling in ROS. When the activity of the CYP2E1 was increased by pyrazole pretreatment, an additional two-fold elevation in ROS was detected. However, the CYP2EIrelated ROS elevation was not accompanied with a correlative increase in apoptotic cell injury, but rather was found to be associated with an increase in necrotic cell death. Interestingly, when the thiol status of the cells was manipulated using BSO, the ethanol-induced activation of caspase-3 was abrogated. Additionally, ethanol-treated cells displayed enhanced susceptibility to Fas-mediated apoptosis that was blocked by GSH depletion as a result of diminished caspase-8 activity. CONCLUSION： Apoptotic cell death induced as a consequence of ethanol metabolism is not completely dependent upon ROS status but is dependent on sustained GSH levels,