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

FEBS Letters

Kupferberg, A.¹  Leray, C.¹  Behr, P.¹  Mersel, M.¹  Urban, P.F.¹ 

[1] Centre de Neurochimie du CNRS et Unitè 44 de l'INSERM, 5 rue Blaise Pascal, 67084 Strasbourg, France

关键词: Astrocyte culture;    7β-Hydroxycholesterol;    Cytotoxicity;    Cholesterogenesis;    3-Hydroxy-3-methylglutaryl CoA reductase;   

DOI  :  10.1016/0014-5793(91)80293-C

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 X₁ and X₂ between mevalonate and CH was found in unsaponifiable neutral lipids extracted from 7β-OH-CH treated transformed cells. HPLC and GC-MS revealed that X₁ and X₂ are not lanosterol anti 24.25-epoxylanosterol, respectively. Incubation of the transformed cells with X₁ and X₂ did 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.

【 授权许可】

Unknown