HMG CoA reductase and LDL receptor genes are regulated differently by 15-ketosterols in Hep G2 cells.
The ability of two 15-ketosubstituted sterols, 5alpha-cholest-8(14)-en-3beta-ol-15-one and 3beta-(2-hydroxyethoxy)-5alpha-cholest-8(14)-en-15-one, to alter the mRNA levels of 3-hydroxy-3-methylglutaryl-CoA reductase, low density lipoprotein receptor, and oxysterol binding protein was studied and compared with the effects of 25-hydroxycholesterol in Hep G2 cells. All three oxysterols decreased the level of HMG CoA reductase mRNA at concentrations of 10-30 microM, although 25-hydroxycholesterol was effective at concentrations of 1-3 microM. 25-Hydroxycholesterol lowered the level of LDL receptor mRNA more efficiently after 8 hours than after 24 hours of incubation, whereas 15-ketosterols did not decrease the mRNA level of the LDL receptor. The transcriptions of HMG CoA reductase and LDL receptor genes are therefore independently regulated by 15-ketosterols in Hep G2 cells. In addition, the level of the oxysterol binding protein mRNA is not affected by oxysterols in Hep G2 cells.
Kisseleva
A F
AF
INSERM, U476, 18, av. Mozart, Marseille, 13009, France.
Goryunova
L E
LE
Planells
R
R
Lafont
H
H
Alquier
C
C
D002460:Cell Line; D002784:Cholesterol / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000235:genetics*; D008099:Liver / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D011973:Receptors, LDL / Q000235:genetics*; D011987:Receptors, Steroid / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013261:Sterols / Q000378:metabolism*; D013997:Time Factors; D000098825:Oxysterol Binding Proteins
D012333:RNA, Messenger; D011973:Receptors, LDL; D011987:Receptors, Steroid; D013261:Sterols; D000098825:Oxysterol Binding Proteins; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases