The MEF2A and MEF2D isoforms are differentially regulated in muscle and adipose tissue during states of insulin deficiency.
Previously we have demonstrated that striated muscle GLUT4 gene expression decreased following streptozotocin-induced diabetes due to a loss of MEF2A transcription factor expression without any significant effect on the MEF2D isoform (Mora, S. and J. E. Pessin (2000) J Biol Chem, 275:16323-16328). In contrast to both cardiac and skeletal muscle, adipose tissue displays a selective decrease in MEF2D expression in diabetes without any significant alteration in MEF2A protein content. Adipose tissue also expresses very low levels of the MEF2 transcription factors and nuclear extracts from white adipose tissue exhibit poor in vitro binding to the MEF2 element. However, addition of in vitro synthesized MEF2A to adipose nuclear extracts results in the formation of the expected MEF2/DNA complex. More importantly, binding to the MEF2 element was also compromised in the diabetic condition. Furthermore, in vivo overexpression of MEF2A selectively in adipose tissue did not affect GLUT4 or MEF2D expression and was not sufficient to prevent GLUT4 down-regulation that occurred in insulin-deficient states.
Mora
S
S
Department of Physiology and Biophysics, The University of Iowa, Iowa City, Iowa 52242, USA.
Yang
C
C
Ryder
J W
JW
Boeglin
D
D
Pessin
J E
JE
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004268:DNA-Binding Proteins / Q000032:analysis* / Q000737:chemistry; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D019281:Dimerization; D051275:Glucose Transporter Type 4; D006801:Humans; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000032:analysis; D009124:Muscle Proteins; D009132:Muscles / Q000378:metabolism*; D018006:Myogenic Regulatory Factors; D020033:Protein Isoforms / Q000032:analysis; D051381:Rats; D013311:Streptozocin; D014157:Transcription Factors / Q000032:analysis* / Q000737:chemistry
D004268:DNA-Binding Proteins; D051275:Glucose Transporter Type 4; D026161:MADS Domain Proteins; D064326:MEF2 Transcription Factors; C578035:MEF2A protein, human; C578043:MEF2D protein, human; C578036:Mef2a protein, mouse; C578044:Mef2d protein, mouse; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D018006:Myogenic Regulatory Factors; D020033:Protein Isoforms; C495692:SLC2A4 protein, human; C495693:Slc2a4 protein, mouse; C495694:Slc2a4 protein, rat; D014157:Transcription Factors; D013311:Streptozocin