Original Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Biol Chem. Dec 26, 2011; 2(12): 252-260
Published online Dec 26, 2011. doi: 10.4331/wjbc.v2.i12.252
Regulation of heme oxygenase expression by alcohol, hypoxia and oxidative stress
Lisa Nicole Gerjevic, Sizhao Lu, Jonathan Pascal Chaky, Duygu Dee Harrison-Findik
Lisa Nicole Gerjevic, Sizhao Lu, Jonathan Pascal Chaky, Duygu Dee Harrison-Findik, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5820, United States
Author contributions: Gerjevic LN, Lu S and and Chaky JP performed the experiments and helped with the manuscript; Harrison-Findik DD designed the study, and wrote and edited the manuscript.
Supported by University of Nebraska Medical Center Funds and NIH grant (R01AA017738) to Harrison-Findik DD
Correspondence to: Duygu Dee Harrison-Findik, DVM, PhD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68198-5820, United States. dharrisonfindik@unmc.edu
Telephone: +1-402-5596355 Fax: +1-402-5596494
Received: March 18, 2011
Revised: October 11, 2011
Accepted: October 17, 2011
Published online: December 26, 2011
Abstract

AIM: To study the effect of both acute and chronic alcohol exposure on heme oxygenases (HOs) in the brain, liver and duodenum.

METHODS: Wild-type C57BL/6 mice, heterozygous Sod2 knockout mice, which exhibit attenuated manganese superoxide dismutase activity, and liver-specific ARNT knockout mice were used to investigate the role of alcohol-induced oxidative stress and hypoxia. For acute alcohol exposure, ethanol was administered in the drinking water for 1 wk. Mice were pair-fed with regular or ethanol-containing Lieber De Carli liquid diets for 4 wk for chronic alcohol studies. HO expression was analyzed by real-time quantitative polymerase chain reaction and Western blotting.

RESULTS: Chronic alcohol exposure downregulated HO-1 expression in the brain but upregulated it in the duodenum of wild-type mice. It did not alter liver HO-1 expression, nor HO-2 expression in the brain, liver or duodenum. In contrast, acute alcohol exposure decreased both liver HO-1 and HO-2 expression, and HO-2 expression in the duodenum of wild-type mice. The decrease in liver HO-1 expression was abolished in ARNT+/- mice. Sod2+/- mice with acute alcohol exposure did not exhibit any changes in liver HO-1 and HO-2 expression or in brain HO-2 expression. However, alcohol inhibited brain HO-1 and duodenal HO-2 but increased duodenal HO-1 expression in Sod2+/- mice. Collectively, these findings indicate that acute and chronic alcohol exposure regulates HO expression in a tissue-specific manner. Chronic alcohol exposure alters brain and duodenal, but not liver HO expression. However, acute alcohol exposure inhibits liver HO-1 and HO-2, and also duodenal HO-2 expression.

CONCLUSION: The inhibition of liver HO expression by acute alcohol-induced hypoxia may play a role in the early phases of alcoholic liver disease progression.

Keywords: Alcohol, Brain, Duodenum, Heme oxygenase, Hypoxia, Iron, Liver, Mitochondria, Oxidative stress, Reactive oxygen species