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Effect of 7β‐hydroxycholesterol on astrocyte primary cultures and derived spontaneously transformed cell lines Cytotoxicity and cholesterogenesis
Author(s) -
Behr P.,
Kupferberg A.,
Leray C.,
Urban P.F.,
Mersel M.
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)80293-c
Subject(s) - cytotoxicity , incubation , cell culture , cytotoxic t cell , reductase , mevalonic acid , biochemistry , chemistry , l1210 cells , microbiology and biotechnology , biology , astrocyte , stereochemistry , enzyme , in vitro , endocrinology , genetics , central nervous system
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 [ 14 C]acetate or [ 14 C] 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 1 and X 2 between mevalonate and CH was found in unsaponifiable neutral lipids extracted from 7β‐OH‐CH treated transformed cells. HPLC and GC‐MS revealed that X 1 and X 2 are not lanosterol anti 24.25‐epoxylanosterol, respectively. Incubation of the transformed cells with X 1 and X 2 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.