Abstract
The regulation of fatty acid synthase (FAS) expression by sterols in a cultured human hepatoblastoma cell line, Hep G2, was studied. When cells were treated with compactin in a medium containing lipoprotein deficient serum, FAS mRNA level increased 1.6-fold. A squalene synthase inhibitor, TAN1607A, decreased both free and esterified cholesterol contents in Hep G2 cells and increased mRNA levels for FAS, HMG-CoA reductase, squalene synthase and LDL receptor. However, for the increment of FAS mRNA, a 10-fold higher concentration of this inhibitor was needed. These results demonstrate that the concentration of cellular cholesterol which regulates FAS expression is necessarily lower than the levels which regulate other sterol sensitive genes. FAS mRNA was also increased by an inhibitor of SREBP degradation as well as chenodeoxycholic acid. These results indicate that FAS mRNA expression is regulated by cholesterol and is mediated through SREBPs. The implications of the different modes of sterol regulation of FAS and LDL receptor expression are discussed.
Citations
Jan 1, 1997·Annual Review of Cell and Developmental Biology·C S HwangM D Lane
May 29, 2012·Biochemical Pharmacology·Emmanuelle Plée-GautierLaurent Corcos
Mar 21, 1998·Metabolism: Clinical and Experimental·C Noel-SubervilleH Garcin
Jun 23, 2004·Prostaglandins, Leukotrienes, and Essential Fatty Acids·P RiséC Galli
Apr 4, 1998·The American Journal of Cardiology·H N Ginsberg
May 1, 2009·BMB Reports·Eun Ju KimJa-Hyun Koo
Jun 27, 2002·Biochemical and Biophysical Research Communications·Masaaki NagaiTeruo Ono
Aug 1, 1998·The Journal of Biological Chemistry·J V SwinnenG Verhoeven
Oct 25, 1996·The Journal of Biological Chemistry·R SatoM Maeda
Jan 5, 2000·Physiological Reviews·G J Schroepfer
Apr 11, 1997·The Journal of Biological Chemistry·G GuanI Shechter
Jun 20, 1998·The Journal of Biological Chemistry·G GuanI Shechter
Aug 26, 1998·The Journal of Biological Chemistry·R A ChouinardA R Tall
May 23, 2001·Archives of Biochemistry and Biophysics·S S WolfM Schweizer
Feb 16, 1999·Biochimica Et Biophysica Acta·Y KawabeT Kodama
Dec 6, 1997·Current Opinion in Genetics & Development·T M Loftus, M D Lane
Jun 11, 1997·European Journal of Pharmacology·T FujiokaH Shimotsu