title: Host homeostatic responses to alcohol-induced cellular stress in animal models of alcoholic liver disease.
abstract: Humans develop various clinical phenotypes of severe alcoholic liver disease, including alcoholic hepatitis and cirrhosis, generally after decades of heavy drinking. In such individuals, following each episode of drinking, their livers experience heightened intracellular and extracellular stresses that are closely associated with alcohol consumption and alcohol metabolism. This article focuses on the latest advances made in animal models on evolutionarily conserved homeostatic mechanisms for coping with and resolving these stress conditions. The mechanisms discussed include the stress-activated protein kinase JNK, energy regulator AMPK, autophagy and the inflammatory response. Over time, the host may respond variably to stress with protective mechanisms that are critical in determining an individual's vulnerability to developing severe alcoholic liver disease. A systematic review of these mechanisms and their temporal changes in animal models provides the basis for general conclusions, and raises questions for future studies. The relevance of these data to human conditions is also discussed.
authors: a Division of Metabolism and Health Effect, National Institute of Alcohol Abuse and Alcoholism/NIH, 5635 Fishers Lane, MSC 9304, Bethesda, MD 20892-9304, USA.
authors: He Joe
authors: HJ
authors: Wang
authors: Gary J
authors: GJ
authors: Murray
authors: Mary Katherine
authors: MK
authors: Jung
mesh_terms: D000428:Alcohol Drinking / Q000009:adverse effects / Q000503:physiopathology*; D000818:Animals; D006706:Homeostasis; D006801:Humans; D008108:Liver Diseases, Alcoholic / Q000503:physiopathology*; D051379:Mice; D023421:Models, Animal; D051381:Rats; D013312:Stress, Physiological
keywords: AMP protein kinase; alcohol metabolism; alcoholic liver disease; animal models; autophagy; c-Jun N-terminal kinases; cellular stress; homeostatic response; macrophage polarity; oxidative stress