Co-ordinate regulation of low-density-lipoprotein receptor and 3-hydroxy-3-methylglutaryl-CoA reductase and synthase gene expression in HepG2 cells.
Cellular processes responsible for maintaining cholesterol homoeostasis are highly regulated. To determine whether two of these processes, cholesterol biosynthesis and receptor-mediated uptake of low-density lipoprotein (LDL), are co-ordinately regulated in human liver, we employed a human hepatoma cell line (HepG2) and measured the accumulation of mRNA for LDL receptor, 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase and HMG-CoA synthase under a variety of conditions. Genomic Southern-blot analysis demonstrated that the integrity of these genes is maintained in the transformed cell. Treatment of HepG2 cells with mevalonate, 25-hydroxycholesterol, LDL, lovastatin or miconazole resulted in a similar effect on the accumulation of all three mRNAs at the concentrations tested. The onset of the response to drug, whether repression or induction of mRNA accumulation, occurred after approximately the same period of exposure for each mRNA. We conclude that the expression of the LDL receptor, HMG-CoA reductase and HMG-CoA synthase is co-ordinately regulated in HepG2 cells.
Molowa
D T
DT
Department of Molecular Pharmacology and Biochemistry, Merck Sharp & Dohme Research Laboratories, Rahway, NJ 07065.
Cimis
G M
GM
D006528:Carcinoma, Hepatocellular / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D006888:Hydroxycholesterols / Q000494:pharmacology; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D006904:Hydroxymethylglutaryl-CoA Synthase / Q000235:genetics*; D008113:Liver Neoplasms / Q000378:metabolism; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology; D007652:Oxo-Acid-Lyases / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011973:Receptors, LDL / Q000235:genetics*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D004273:DNA, Neoplasm; D006888:Hydroxycholesterols; D012333:RNA, Messenger; D011973:Receptors, LDL; C007997:25-hydroxycholesterol; D008148:Lovastatin; D006903:Hydroxymethylglutaryl CoA Reductases; D006904:Hydroxymethylglutaryl-CoA Synthase; D007652:Oxo-Acid-Lyases; D008798:Mevalonic Acid