Abstract
Feeding rats diets containing 2% cholesterol markedly reduced hepatic 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity but had little effect on mRNA levels. Addition of mevalonolactone to the diet further decreased reductase activity independent of a change in mRNA levels. In contrast, farnesyl pyrophosphate synthetase mRNA levels and enzyme activity were decreased to similar degrees in response to dietary cholesterol. Addition of mevalonolactone to the diet did not further decrease farnesyl pyrophosphate synthetase activity. Dietary cholesterol and mevalonolactone had no effect on mRNA levels for "cellular nucleic acid-binding protein" which has been demonstrated to bind the sterol regulatory elements in the HMG-CoA reductase and farnesyl pyrophosphate synthetase promoters. Dietary cholesterol increased cholesterol 7 alpha-hydroxylase mRNA levels as expected. These results suggest that cholesterol-mediated feed-back regulation of hepatic HMG-CoA reductase gene expression does not occur at the level of transcription.
Highlights
Hydroxy-3-methylglutaryl-CoA Reductase Activity by Dietary fold amplification of the reductase gene [13]
By extrapolation it was concluded that. These results suggest that cholesterol-mediated feed- dietary cholesterol acted to decrease HMG-CoA reductase back regulation of hepatic HMG-CoA reductase gene mRNA levels in normally fed rats [16]
The design of the experiments reported herewas based on previous studies in culturedcells which indicated that sterols levels of hepatic HMC-CoA reductase (HMCR) and farnesyl pyrophosphate synthetase(FI'PS) mRNA
Summary
HMG-CoA’ reductase, an integral membrane protein of the of HMG-CoA reductase under uninduced conditions, we have endoplasmic reticulum, catalyzes the rate-limiting reaction in reinvestigated the effect of cholesterol feeding on reductase the biosynthesis of cholesterol [1].It has long been recognized mRNA levels in normal rats using a Northern blotting assay that feeding cholesterol to animals markedly reduces the rate which allows for greatly increased detection. Of hepatic cholesterol biosynthesis [2,3,4,5]. This isdue primarily we found that while cholesterol feeding greatly diminished to decreased HMG-CoA reductase activity [6,7,8,9,10]. The mechanism by which cholesterol actsto decrease effect on reductase mRNA levels. HMG-CoA reductase activity has been the subject of extensive investigation [11].In a recent review, it was concluded
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
