Gene regulation of de novo cholesterol synthesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (Meeting abstract). NLM AIDSLINE Important note: Information in this article was accurate in 1997. The state of the art may have changed since the publication date.

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Gene regulation of de novo cholesterol synthesis by 2,3,7,8-tetrachlorodibenzo-p-dioxin (Meeting abstract).

Proc Annu Meet Am Assoc Cancer Res; 38:A416 1997. Unique Identifier : AIDSLINE MED/97619102
Tian Y; Ke S; Germino JF; Meeker R; and Gallo MA; UMDNJ-Robert Wood Johnson Medical School, Piscataway, NJ 08855

Abstract: The aryl hydrocarbon (Ah) receptor which is a ligand activated basic HLH transcription factor. The most potent ligand 2,3,7,8-TCDD, is a tumor promoter that dramatically alters lipid profiles in rodents. TCDD, at 1 ug/kg, causes a significant inhibition of cholesterol synthesis in liver and adipose tissue in rats. We studied the effects of TCDD on de novo cholesterol biosynthesis by evaluating the changes of gene expression of HMG-CoA reductase, a key enzyme in cholesterol synthesis. Human HepG2 cells were treated with 10 nM TCDD and HMG CoA reductase mRNA was evaluated by semiquantitative RT-PCR. Under these conditions, TCDD significantly decreased (more than 50%) mRNA of the reductase (after 6 hours and through 24 hours). In a gel mobility shift assay, TCDD decreased the binding of sterol response element binding protein (SREBP), which is also a HLH protein, to a synthetic sterol response element (SRE-1). These results suggest that TCDD disrupts gene expression of HMG CoA reductase at the transcription level, perhaps, through competition for a common limiting factor. The transcriptional down regulation of HMG CoA reductase may contribute to the inhibition of de novo cholesterol synthesis.
Keywords: *Anti-HIV Agents/METABOLISM *Carrier Proteins/METABOLISM *Mitochondria/METABOLISM *Nucleotides/METABOLISMKWDanti-hivagents/metabolismKWDcarrierproteins/metabolismKWDmitochondria/metabolismKWDnucleotides/metabolism
971030
M97A1342

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