Endoplasmic Reticulum Stress and Liver Injury

Neil Kaplowitz; Tin Aung Than; Masao Shinohara; Cheng Ji

doi:10.1055/s-2007-991513

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2007; 27(4): 367-377
DOI: 10.1055/s-2007-991513

Endoplasmic Reticulum Stress and Liver Injury

Neil Kaplowitz¹ , Tin Aung Than¹ , Masao Shinohara¹ , Cheng Ji¹

¹Department 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

Abstract

ABSTRACT

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.

KEYWORDS

Unfolded protein response - fatty liver - apoptosis - hyperhomocysteinemia - chaperones.

Full Text

References

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Neil KaplowitzM.D.

Professor of Medicine, Keck School of Medicine

University of Southern California, 2011 Zonal Avenue, HMR 101, Los Angeles, CA 90033

Email: kaplowit@usc.edu