New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases

Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stres...

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Main Author: Cheng Ji
Format: Article
Language:English
Published: Wiley 2014-01-01
Series:International Journal of Hepatology
Online Access:http://dx.doi.org/10.1155/2014/513787
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author Cheng Ji
author_facet Cheng Ji
author_sort Cheng Ji
collection DOAJ
description Alcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.
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spelling doaj-art-88cd03f3e54e44c0a6f1bbffe5376c722025-08-20T03:38:05ZengWileyInternational Journal of Hepatology2090-34482090-34562014-01-01201410.1155/2014/513787513787New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver DiseasesCheng Ji0USC Research Center for Liver Disease, Department of Medicine, Keck School of Medicine of USC, University of Southern California, 2011 Zonal Avenue, HMR-101, Los Angeles, CA 90089, USAAlcohol-induced liver disease increasingly contributes to human mortality worldwide. Alcohol-induced endoplasmic reticulum (ER) stress and disruption of cellular protein homeostasis have recently been established as a significant mechanism contributing to liver diseases. The alcohol-induced ER stress occurs not only in cultured hepatocytes but also  in vivo  in the livers of several species including mouse, rat, minipigs, zebrafish, and humans. Identified causes for the ER stress include acetaldehyde, oxidative stress, impaired one carbon metabolism, toxic lipid species, insulin resistance, disrupted calcium homeostasis, and aberrant epigenetic modifications. Importance of each of the causes in alcohol-induced liver injury depends on doses, duration and patterns of alcohol exposure, genetic disposition, environmental factors, cross-talks with other pathogenic pathways, and stages of liver disease. The ER stress may occur more or less all the time during alcohol consumption, which interferes with hepatic protein homeostasis, proliferation, and cell cycle progression promoting development of advanced liver diseases. Emerging evidence indicates that long-term alcohol consumption and ER stress may directly be involved in hepatocellular carcinogenesis (HCC). Dissecting ER stress signaling pathways leading to tumorigenesis will uncover potential therapeutic targets for intervention and treatment of human alcoholics with liver cancer.http://dx.doi.org/10.1155/2014/513787
spellingShingle Cheng Ji
New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases
International Journal of Hepatology
title New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases
title_full New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases
title_fullStr New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases
title_full_unstemmed New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases
title_short New Insights into the Pathogenesis of Alcohol-Induced ER Stress and Liver Diseases
title_sort new insights into the pathogenesis of alcohol induced er stress and liver diseases
url http://dx.doi.org/10.1155/2014/513787
work_keys_str_mv AT chengji newinsightsintothepathogenesisofalcoholinducederstressandliverdiseases