TRANSCRIPTIONAL REGULATION OF SQUALENE EPOXIDASE BY STEROLS AND INHIBITORS IN HELA-CELLS

Regulation of squalene epoxidase (SE) gene expression was studied in c omparison with those of 5-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reduc tase and low density lipoprotein (LDL) receptor. An increased expressi on of SE mRNA and protein content in mouse L929 cells grown in 10% lip oprotein-deficient fetal bovine serum (LPDS) for 48 h was found by per forming immunoblot and Northern blot analyses when compared with the c ulture in the presence of fetal bovine serum (FBS). The same results i n mRNA levels were seen using human cell lines HepG2, HeLa, and Chang liver cells. The increase of SE mRNA in HeLa cells grown in LPDS was p reventable in a dose-dependent manner by feeding cells with 25-hydroxy cholesterol or cholesterol. When an SE inhibitor, NB-598, was fed to H eLa cells grown in LPDS, it caused further increases in mRNA levels of SE, HMG-CoA reductase, and LDL receptor. In contrast, NB-598 had no e ffect on the message levels of these genes when fed to HeLa cells grow n in FBS. These results suggest that sterol produced endogenously can also regulate SE expression at the level of transcription.