Transcriptional regulation of the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene in rat liver
| Autor: | C F, Clarke, A M, Fogelman, P A, Edwards |
|---|---|
| Rok vydání: | 1985 |
| Předmět: |
Cell Nucleus
Male Amanitins Transcription Genetic Cholestyramine Resin Mevalonic Acid Nucleic Acid Hybridization Rats Inbred Strains Naphthalenes Rats Liver Microsomes Liver Animals Hydroxymethylglutaryl CoA Reductases Lovastatin RNA Polymerase II RNA Messenger Hydroxymethylglutaryl-CoA Reductase Inhibitors |
| Zdroj: | The Journal of biological chemistry. 260(26) |
| ISSN: | 0021-9258 |
| Popis: | This study addresses whether transcriptional control of the 3-hydroxy-3-methylglutaryl coenzyme A reductase gene in rat liver plays a role in determining the level of reductase mRNA. Isolated rat liver nuclei were allowed to elongate nascent RNA transcripts in the presence of [alpha-32P]CTP, and radiolabeled nuclear reductase RNA was quantitated by filter hybridization. Rats fed a diet supplemented with the drugs cholestyramine and mevinolin and having 20-60-fold induced levels of reductase mRNA exhibited levels of reductase transcription which were 20-fold higher than in rats fed an unsupplemented diet. Over 90% of the transcription of the reductase gene was inhibited by concentrations of alpha-amanitin which selectively inhibit RNA polymerase II. Administration of mevalonolactone (the end product of the reaction catalyzed by reductase) to rats fed cholestyramine and mevinolin caused an 80% decrease in the rate of reductase transcription by approximately 1 h. We conclude that under these conditions changes in reductase transcription are primarily responsible for the regulation of reductase mRNA levels. |
| Databáze: | OpenAIRE |
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