Sterol-mediated suppression of HMG-CoA reductase mRNA levels in cultured cells requires protein synthesis.
The mRNA levels for HMG-CoA reductase were measured in Chinese hamster lung Dede cells or ovary CHO cells by Northern blot analysis. It was observed that 25-hydroxycholesterol decreased the level of reductase mRNA by 40 to 70% in a 6 hour treatment. Inclusion of cycloheximide in the culture prevented the decrease observed with 25-hydroxycholesterol alone. Pretreatment of cells with 25-hydroxycholesterol for 6 hours prior to cycloheximide addition reveals that the protein synthesis inhibitor can return the suppressed levels of reductase mRNA back to control levels. Thus, protein synthesis is required for 25-hydroxycholesterol dependent suppression of HMG-CoA reductase mRNA.
Trzaskos
J M
JM
Medical Products Department, E. I. du Pont de Nemours and Co., Inc., Wilmington, DE 19880-0400.
Jonas
M
M
Chen
H W
HW
D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D003513:Cycloheximide / Q000494:pharmacology; D005260:Female; D006888:Hydroxycholesterols / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D007700:Kinetics; D010053:Ovary; D014176:Protein Biosynthesis; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis / Q000187:drug effects*
D006888:Hydroxycholesterols; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; C007997:25-hydroxycholesterol; D003513:Cycloheximide