Endoplasmic reticulum stress and liver injury.
Endoplasmic reticulum stress, initiated by protein overload or malfolding, activates a complex network of interacting and parallel responses that dampen the stress. However, when the protective response is insufficient, a set of responses leads to apoptosis. Coupled with the latter are promotion of lipid synthesis and proinflammatory responses. Evidence has been mounting for an important role of the endoplasmic reticulum (ER) stress response in the pathogenesis of chronic viral hepatitis, insulin resistance and nonalcoholic fatty liver disease, ischemia-reperfusion injury, genetic disorders of protein malfolding, and alcoholic liver disease. In the latter, a key candidate for inducing ER stress is hyperhomocysteinemia. Betaine treatment promotes removal of homocysteine and prevents ER stress, fatty liver, and apoptosis in a mouse model of alcohol-induced liver disease. With increasing interest in the potential role of ER stress in liver disease, greater understanding of pathophysiology, prevention, and treatment of liver disease is anticipated.
Kaplowitz
Neil
N
Department of Medicine, USC-UCLA Research Center for Alcoholic and Pancreatic Diseases and USC Research Center for Liver Diseases, Keck School of Medicine University of Southern California, Los Angeles, California CA 90033, USA. kaplowit@usc.edu
Than
Tin Aung
TA
Shinohara
Masao
M
Ji
Cheng
C
D000818:Animals; D017209:Apoptosis; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D006801:Humans; D020138:Hyperhomocysteinemia / Q000378:metabolism; D008099:Liver / Q000293:injuries / Q000378:metabolism; D008107:Liver Diseases / Q000378:metabolism* / Q000473:pathology; D008954:Models, Biological