Stimulation of HMG-CoA reductase as a consequence of phenobarbital-induced primary stimulation of cholesterol 7 alpha-hydroxylase in rat liver
| Autor: | Ingemar Björkhem, Elly Sudjana-Sugiaman, Gösta Eggertsen |
|---|---|
| Rok vydání: | 1994 |
| Předmět: |
Male
medicine.medical_specialty Stimulation QD415-436 Biology Reductase Cholesterol 7 alpha-hydroxylase Biochemistry Rats Sprague-Dawley chemistry.chemical_compound Endocrinology Internal medicine medicine Animals Rats Wistar Cholesterol 7-alpha-Hydroxylase Cholesterol Cytochrome P450 Rats Inbred Strains Cell Biology Blotting Northern Rats Liver chemistry Phenobarbital HMG-CoA reductase Microsomes Liver Microsome biology.protein RNA Hydroxymethylglutaryl CoA Reductases Subcellular Fractions medicine.drug |
| Zdroj: | Europe PubMed Central Journal of Lipid Research, Vol 35, Iss 2, Pp 319-327 (1994) |
| ISSN: | 0022-2275 |
| DOI: | 10.1016/s0022-2275(20)41206-4 |
| Popis: | Among nine strains of rat, two were found that responded to phenobarbital treatment with increased activity of hepatic cholesterol 7 alpha-hydroxylase. This effect was maximal after 2-3 days of treatment and was then reduced. Interestingly the increased cholesterol 7 alpha-hydroxylase activity was associated with increased activity of hepatic HMG-CoA reductase in the two responding strains but not in the non-responding strains. In tissues other than the liver, HMG-CoA reductase activity was unaffected in responding rats. Most of the above stimulation occurred at a pretranslatory level and the mRNA levels corresponding to the two enzymes paralleled the activities. The phenobarbital treatment resulted in decreased content of free cholesterol in liver microsomes in a strain of rat that responded with increased cholesterol 7 alpha-hydroxylase activity. It was shown that depletion of cholesterol in the responding strain of rats by lymph fistulation also was associated with a parallel increase in levels of HMG-CoA reductase activity and mRNA. The findings are discussed in relation to the link between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase. A primary upregulation of the cholesterol 7 alpha-hydroxylase by the cytochrome P450 inducer phenobarbital can be expected to lead to increased consumption of cholesterol substrate. This consumption may result in a compensatory increase in the activity of the HMG-CoA reductase. It is suggested that such a mechanism is responsible for part of the covariation of the two enzyme systems under different conditions. |
| Databáze: | OpenAIRE |
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