Popják G, Meenan A, Nes W D
Department of Medicine, U.C.L.A. School of Medicine 90024.
Proc R Soc Lond B Biol Sci. 1987 Dec 22;232(1268):273-87. doi: 10.1098/rspb.1987.0074.
2,3-Iminosqualene (ISq) is a powerful inhibitor of squalene oxide:lanosterol cyclase (EC 5.4.99.7). When added to lipid-depleted culture media (LDM) of rat hepatoma (H-4-II-E-C3) or Chinese hamster ovary (CHO) cells at a concentration of 10 micrograms ml-1, it causes the cells to float off the substratum in a few days. Lipoproteins in the culture medium completely counteract this effect. Cells in lipoprotein-containing media (FGM) grow normally in the presence of ISq. Irrespective of the culture medium, ISq at 10 micrograms ml-1 causes an almost complete and apparently irreversible inactivation of the squalene oxide cyclase in CHO and H4 cells and the accumulation in the cells of squalene, of squalene 2,3-oxide (mostly), and of squalene 2,3-22,23-dioxide when [14C]acetate or [14C]mevalonate is fed to the cells. Chronic treatment of H4 cells with ISq failed to elicit induction of the cyclase, but increased the conversion of mevalonate into squalene and squalene dioxide, and depressed the conversion of squalene oxide to the dioxide. Cells loaded with squalene and the squalene oxides from mevalonate in the presence of ISq get rid of these substances by rapidly secreting them into the media and by some unidentified metabolic processes.
2,3-亚氨基角鲨烯（ISq）是氧化角鲨烯：羊毛甾醇环化酶（EC 5.4.99.7）的强效抑制剂。当以10微克/毫升的浓度添加到大鼠肝癌（H-4-II-E-C3）或中国仓鼠卵巢（CHO）细胞的脂质耗尽培养基（LDM）中时，它会在几天内使细胞从基质上漂浮起来。培养基中的脂蛋白可完全抵消这种作用。在含脂蛋白的培养基（FGM）中，细胞在ISq存在的情况下能正常生长。无论培养基如何，10微克/毫升的ISq会导致CHO细胞和H4细胞中的氧化角鲨烯环化酶几乎完全且明显不可逆地失活，并使角鲨烯、2,3-氧化角鲨烯（主要是）以及2,3-22,23-二氧化角鲨烯在细胞中积累，前提是向细胞投喂[14C]乙酸盐或[14C]甲羟戊酸。用ISq对H4细胞进行长期处理未能诱导环化酶的产生，但增加了甲羟戊酸向角鲨烯和二氧化角鲨烯的转化，并抑制了氧化角鲨烯向二氧化角鲨烯的转化。在ISq存在的情况下，从甲羟戊酸加载了角鲨烯和氧化角鲨烯的细胞通过迅速将这些物质分泌到培养基中以及一些不明代谢过程来清除它们。
