Differential regulation of hepatic triglyceride lipase and 3-hydroxy-3-methylglutaryl-CoA reductase gene expression in a human hepatoma cell line, HepG2
| Autor: | Richard L. Jackson, M A Flanagan, Roger L. Barnhart, G A Martin, S J Busch |
|---|---|
| Rok vydání: | 1990 |
| Předmět: |
7-Dehydrocholesterol reductase
medicine.medical_specialty Triglyceride lipase biology Cholesterol Cell Biology Mevalonic acid Reductase Biochemistry Hydroxymethylglutaryl-CoA reductase chemistry.chemical_compound Endocrinology chemistry Biosynthesis Internal medicine HMG-CoA reductase medicine biology.protein Molecular Biology |
| Zdroj: | Journal of Biological Chemistry. 265:22474-22479 |
| ISSN: | 0021-9258 |
| DOI: | 10.1016/s0021-9258(18)45729-8 |
| Popis: | The level of hepatic triglyceride lipase (H-TGL) synthesis and secretion was examined in response to changes in cholesterol biosynthesis in the human hepatoma cell line HepG2. Cells were first fed a lipoprotein-deficient serum-supplemented medium to eliminate exogenous cholesterol. Mevinolin, a 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase inhibitor, was then added at a concentration (37 microM) which inhibited cholesterol biosynthesis by greater than 85% and decreased total cell cholesterol from 36.1 to 27.4 micrograms/ml of cell protein. Mevinolin treatment caused a 4.9 +/- 0.8-fold increase in the amount of H-TGL activity secreted into the medium, a 1.8 +/- 0.4-fold rise in H-TGL-specific mRNA, and a concurrent 14-fold increase in HMG-CoA reductase mRNA. Addition of 1 mM mevalonic acid to normal or mevinolin-treated cells raised the cellular cholesterol content and decreased the amount of secreted H-TGL activity to levels below control values. Mevalonic acid also prevented mevinolin-induction of H-TGL and HMG-CoA reductase mRNA, suggesting a common regulatory step for H-TGL and HMG-CoA reductase. Exposure of cells to mevinolin and 25-hydroxycholesterol together resulted in a marked repression of HMG-CoA reductase mRNA levels, whereas these conditions further enhanced the secretion of H-TGL activity and the expression of H-TGL mRNA. These results demonstrate a differential role for 25-hydroxycholesterol in the regulation of H-TGL and HMG-CoA reductase expression. |
| Databáze: | OpenAIRE |
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