Kawabe Y, Sato R, Matsumoto A, Honda M, Wada Y, Yazaki Y, Endo A, Takano T, Itakura H, Kodama T
Third Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Japan.
Biochem Biophys Res Commun. 1996 Feb 15;219(2):515-20. doi: 10.1006/bbrc.1996.0265.
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.
研究了在培养的人肝癌细胞系Hep G2中，固醇对脂肪酸合酶（FAS）表达的调节作用。当细胞在含有脂蛋白缺陷血清的培养基中用康帕丁处理时，FAS mRNA水平增加了1.6倍。角鲨烯合酶抑制剂TAN1607A降低了Hep G2细胞中游离胆固醇和酯化胆固醇的含量，并增加了FAS、HMG-CoA还原酶、角鲨烯合酶和低密度脂蛋白受体的mRNA水平。然而，对于FAS mRNA的增加，需要该抑制剂浓度高10倍。这些结果表明，调节FAS表达的细胞胆固醇浓度必然低于调节其他固醇敏感基因的水平。FAS mRNA也因SREBP降解抑制剂以及鹅去氧胆酸而增加。这些结果表明，FAS mRNA表达受胆固醇调节，并通过SREBPs介导。讨论了FAS和低密度脂蛋白受体表达的不同固醇调节模式的意义。
