TCDD suppresses insulin-responsive glucose transporter (GLUT-4) gene expression through C/EBP nuclear transcription factors in 3T3-L1 adipocytes

Journal of Biochemical and Molecular Toxicology
Phillip C C Liu, Fumio Matsumura

Abstract

TCDD is known to reduce significantly the level of the functionally active form of glucose transporter type 4 (GLUT4) in vivo in adipose tissue and muscles. To study the mechanistic basis of this phenomenon, we conducted transient transfection and DNA deletion analysis in 3T3-L1 cells using chloramphenicol acetyltransferase (CAT) reporter plasmids containing the GLUT4 promoter joined to the bacterial CAT. It was found that in transfected control samples, CAT activity was significantly higher in cells transfected with p469CAT and p273CAT than those with p78CAT, indicating that the region between -78 and -273 contained elements that play major roles in transactivation of this gene. Treatment with TCDD decreased CAT activity with p469CAT and p273CAT, but not with p78CAT, indicating the same region to contain the element(s) affected by TCDD. A gel-shift (EMSA) analysis result indicated that TCDD shows the profound effect only on the nuclear proteins binding to the [(32)P]-labeled probe containing C/EBP response element equivalent of the -265 to -242 stretch of the GLUT4 promoter. The results of supershift analysis showed that TCDD caused a decrease in the tier of C/EBPalpha and an increase in that of C/EBPbeta among the proteins bo...Continue Reading

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Citations

Apr 15, 2008·The Journal of Biological Chemistry·Hyuk C ChaOrmond A MacDougald
Feb 26, 2010·Toxicological Sciences : an Official Journal of the Society of Toxicology·Shin NishiumiHitoshi Ashida
Nov 16, 2012·Toxicological Sciences : an Official Journal of the Society of Toxicology·Lawrence H KennedyThomas R Sutter
Oct 6, 2012·Drug and Chemical Toxicology·Anne Augustine WilliamsKarundevi Balasubramanian
May 8, 2014·Reproductive Sciences·Kenan OmurtagKelle H Moley

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