Effect of 7β-hydroxycholesterol on astrocyte primary cultures and derived spontaneously transformed cell lines Cytotoxicity and cholesterogenesis

Autor: Behr, P., Kupferberg, A., Leray, C., Urban, P.F., Mersel, M.
Zdroj: FEBS Letters; January 1991, Vol. 280 Issue: 2 p202-206, 5p
Abstrakt: The correlation between the lethal effect of 7β-hydroxycholesterol (7β-OH-CH) on spontaneously transformed cell lines derived from rat astrocyte primary cultures (normal cells) and de novo cholesterogenesis was investigated. Both 7β-OH-CH and 7-keto-CH were not cytotoxic on normal cells but 7β-OH-CH affected markedly the viability of the transformed cells. The use of [ 14C]acetate or [ 14C] mevalonate indicated that 7-keto-CH inhibits de novo cholesterogenesis upstream of 3-hydroxy-3-methylglutaryl CoA reductase (HMGR) in both cell types whereas 7β-OH-CH also inhibits downstream of HMGR. The accumulation of two radiolabelled products X 1and X 2between mevalonate and CH was found in unsaponifiable neutral lipids extracted from 7β-OH-CH treated transformed cells. HPLC and GC-MS revealed that X 1and X 2are not lanosterol anti 24.25-epoxylanosterol, respectively. Incubation of the transformed cells with X 1and X 2did not affect their viability. Our data demonstrate that, under our experimental conditions, 7β-OH-CH cytotoxicity is not linked to the inhibition of de novo cholesterogenesis in cultured glial transformed cells.
Databáze: Supplemental Index