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KMID : 1160620000050040184
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Preventive Nutrition and Food Science
2000 Volume.5 No. 4 p.184 ~ p.188
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Regulation of HMG-CoA Reductase mRNA Stability by 25-hydroxycholesterol
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Park Jae-Won
Oh Seung-Min
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Abstract
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HMG-CoA reductase is the rate-limiting enzyme of cholesterol biosynthesis. As intracellular levels of cholesterol should be regulated elaborately in response to external stimuli and internal needs, the expression of the HMG-CoA reductase gene is regulated intricately at several different levels from transcription to post-translational modification. In this study, we investigated the regulatory mechanism of HMG-CoA reductase gene expression at the post-transcriptional/pre-translational levels in a baby hamster kidney cell line, C100. When 25-hydroxycholesterol was added to cells cultured in medium containing 5% delipidized fetal bovine serum and 25 μM lovastatin, the levels of HMGCoA reductase mRNA decreased rapidly, which seemed to be due to the increased degradation of reductase mRNA. These suppressive effects of 25-hydroxycholesterol on HMG-CoA reductase mRNA levels were blocked by a translation inhibitor, cycloheximide. Similarly, actinomycin D and 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole, transcription inhibitors, blocked the 25-hydroxycholesterol-mediated degradation of HMG-CoA reductase mRNA. These results indicate that new protein/RNA synthesis is required for the degradation of HMG-CoA reductase mRNA. In addition, data from the transfection experiments shows that cis-acting determinants, regulating the stability of reductase mRNA, were scattered in the sequence corresponding to 1766-4313 based on the sequence of Syrian hamster HMG-CoA reductase cDNA. Our data suggests that sterol-mediated destabilization of reductase mRNA might be one of the important regulatory mechanisms of HMG-CoA reductase gene expression.
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KEYWORD
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HMG-CoA recutase, mRNA stability
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