Brief Article
Copyright ©2011 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Hepatol. Sep 27, 2011; 3(9): 250-255
Published online Sep 27, 2011. doi: 10.4254/wjh.v3.i9.250
Binge ethanol intake in chronically exposed rat liver decreases LDL-receptor and increases angiotensinogen gene expression
Annayya R Aroor, Shivendra D Shukla
Annayya R Aroor, Shivendra D Shukla, Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 65212, United States
Author contributions: Aroor AR and Shukla SD designed the study, interpreted the data and wrote the manuscript; Shukla SD supervised the work and critically monitored its development.
Supported by (in part) NIH grant AA11962
Correspondence to: Shivendra D Shukla, PhD, Department of Medical Pharmacology and Physiology, University of Missouri School of Medicine, Columbia, MO 65212, United States.
Telephone: +1-573-8822740 Fax: +1-573-8844558
Received: January 3, 2011
Revised: July 6, 2011
Accepted: August 10, 2011
Published online: September 27, 2011

AIM: To investigated the status of low-density lipoprotein (LDL)-receptor and angiotensionogen gene expression in rats treated chronically with ethanol followed by binge administration, a model that mimics the human scenario.

METHODS: Rats were chronically treated with ethanol in liquid diet for 4 wk followed by a single binge mode of ethanol administration (5 mg/kg body weight). Samples were processed 4 h after binge ethanol administration (chronic ethanol binge). Control rats were fed isocaloric diet. In the control for binge, ethanol was replaced by water. Expression of mRNA for angiotensinogen, c-fos and LDL-receptor, and nuclear accumulation of phospho-extracellular regulated kinases (ERK)1/2 and ERK1/2 protein were examined.

RESULTS: Binge ethanol administration in chronically treated rats caused increase in steatosis and necrosis. Chronic ethanol alone had negligible effect on mRNA levels of LDL-receptor, or on the levels of nuclear ERK1/2 and phospho-ERK1/2. But, chronic ethanol followed by binge caused a decrease in LDL-receptor mRNA, and also decreased the levels of ERK1/2 and phospho-ERK1/2 in the nuclear compartment. On the other hand, chronic ethanol-binge increased mRNA expression of angiotensinogen and c-fos.

CONCLUSION: Binge ethanol after chronic exposure, causes transcriptional dysregulation of LDL-receptor and angiotensinogen genes, both cardiovascular risk factors.

Keywords: Alcoholic liver injury, Angiotensinogen, Ethanol binge, Extracellular regulated kinases1/2, Low-density lipoproteun-receptor, Plasminogen activator inhibitor-1