title: Regulation of the effects of CYP2E1-induced oxidative stress by JNK signaling.
abstract: The generation of excessive amounts of reactive oxygen species (ROS) leads to cellular oxidative stress that underlies a variety of forms of hepatocyte injury and death including that from alcohol. Although ROS can induce cell damage through direct effects on cellular macromolecules, the injurious effects of ROS are mediated largely through changes in signal transduction pathways such as the mitogen-activated protein kinase c-Jun N-terminal kinase (JNK). In response to alcohol, hepatocytes have increased levels of the enzyme cytochrome P450 2E1 (CYP2E1) which generates an oxidant stress that promotes the development of alcoholic steatosis and liver injury. These effects are mediated in large part through overactivation of JNK that alters cell death pathways. Targeting the JNK pathway or its downstream effectors may be a useful therapeutic approach to the oxidative stress generated by CYP2E1 in alcoholic liver disease.
authors.affiliation: I. Department of Medicine, University Medical Center of the Johannes Gutenberg University, 55131 Mainz, Germany.
authors.forename: Jörn M
authors.initials: JM
authors.lastname: Schattenberg
authors.affiliation: Department of Medicine and Marion Bessin Liver Research Center, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA. Electronic address: mark.czaja@einstein.yu.edu.
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Czaja
mesh_terms: D000818:Animals; D016923:Cell Death; D019392:Cytochrome P-450 CYP2E1 / Q000235:genetics / Q000378:metabolism*; D005234:Fatty Liver / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058990:Molecular Targeted Therapy; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D017382:Reactive Oxygen Species; D019392:Cytochrome P-450 CYP2E1; D048031:JNK Mitogen-Activated Protein Kinases
keywords: Alcoholic liver disease; Cytochrome P450 2E1; Mitogen-activated protein kinases; Oxidative stress; c-Jun N-terminal kinase