Exp Mol Med.  2010 Mar;42(3):205-215. 10.3858/emm.2010.42.3.021.

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

• Chen L
• Wang F
• Sun X
• Zhou J
• Gao L
• Jiao Y
• Hou X
• Qin C
• Zhao J

• KMID: 946653
• DOI: http://doi.org/10.3858/emm.2010.42.3.021

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(-1)) for 2 h. II: Rats received different dose (0.5, 2.5 or 5 g.kg(-1).d(-1)) 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.

Keyword

AMP-activated protein kinases; ethanol; glucose transporter type 4; myocardium; myocyte-specific enhancer-binding factor 2

MeSH Terms

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
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