Chronic ethanol feeding impairs AMPK and MEF2 expression and is associated with GLUT4 decrease in rat myocardium.

Abstract

Chronic and heavy alcohol consumption is one of the causes of heart diseases. However, the effects of ethanol on insulin sensitivity in myocardium has been unclear. To investigate the effects of ethanol on the expression of AMP-activated protein kinase (AMPK), myocyte enhancer factor 2 (MEF2) and glucose transporter 4 (GLUT4), all of which are involved in the regulation of insulin sensitivity, in the myocardium, we performed three parts of experiments in vivo and in vitro. I: Rats were injected with 5-amino-4-imidazolecarboxamide ribonucleotide (AICAR, 0.8 mg.kg(-l)) for 2 h. II: Rats received different dose (0.5, 2.5 or 5 g.kg(-l).d(-l)) of ethanol for 22-week. III: Primary neonatal rat cardiomyocytes were isolated and treated with or without 100 mM ethanol or 1 mM AICAR for 4 h. The cardiac protein and mRNA expression of AMPKalpha subunits, MEF2 and GLUT4 were observed by western-blotting and RT-PCR, respectively. Serum TNFalpha levels were assessed by ELISA. The results showed chronic ethanol exposure induced insulin resistance. Ethanol decreased the mRNA levels of AMPKalpha1 and alpha2, the protein levels of total- and phospho-AMPKalpha in cardiomyocytes. Similarly, ethanol showed inhibitory effects on both the mRNA and protein levels of MEF2A and 2D, and GLUT4 in a dose-response-like fashion. Correlation analysis implied an association between phospho-AMPKalpha and MEF2A or MEF2D, and between the levels of MEF2 protein and GLUT4 transcription. In addition, ethanol elevated serum TNFalpha level. Taken together, chronic ethanol exposure decreases the expression of AMPKalpha and MEF2, and is associated with GLUT4 decline in rat myocardium.

• Authors: LiYong Chen, FuRong Wang, XiangLan Sun, Jing Zhou, Ling Gao, YuLian Jiao, XiaoLei Hou, Cheng Yong Qin, JiaJun Zhao
• Journal: Experimental & molecular medicine (Exp Mol Med) Vol. 42 Issue 3 Pg. 205-15 (Mar 31 2010) ISSN: 2092-6413 [Electronic] United States
• PMID: 20164678 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucose Transporter Type 4
• Insulin
• MEF2 Transcription Factors
• Myogenic Regulatory Factors
• Protein Isoforms
• RNA, Messenger
• Ribonucleotides
• Slc2a4 protein, rat
• Tumor Necrosis Factor-alpha
• Aminoimidazole Carboxamide
• Ethanol
• AMP-Activated Protein Kinases
• AICA ribonucleotide

Topics

• AMP-Activated Protein Kinases (genetics, metabolism)
• Aminoimidazole Carboxamide (analogs & derivatives, pharmacology)
• Animals
• Enzyme Activation (drug effects)
• Ethanol (administration & dosage, pharmacology)
• Feeding Behavior (drug effects)
• Gene Expression Regulation (drug effects)
• Glucose Transporter Type 4 (genetics, metabolism)
• Insulin (pharmacology)
• Insulin Resistance
• MEF2 Transcription Factors
• Male
• Myocardium (enzymology)
• Myogenic Regulatory Factors (antagonists & inhibitors, genetics, metabolism)
• Protein Isoforms (antagonists & inhibitors, genetics, metabolism)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Ribonucleotides (pharmacology)
• Time Factors
• Tumor Necrosis Factor-alpha (blood)