Effects of 2,3-iminosqualene in cultured cells
2,3-Iminosqualene added to culture media 10 ug/ml) of rat hepatoma (H4-II-E-C3) or Chinese hamster ovary (CHO) cells irreversibly inactivates the squalene-oxide: lanosterol cyclase, but it does not inhibit general polyprenyl synthesis either from (/sup 14/C)acetate or (/sup 14/C)mevalonate. Isq added to lipoprotein-containing media of H4 cells causes in 24 hr an over twofold rise in HMG-CoA reductase and abolishes the repressive effect of mevalonate (MVA) on the reductase. H4 cells synthesize from (2-/sup 14/C)-MVA labelled squalene, squalene-2,3-oxide, squalene-2,3-22,23-dioxide, but very little sterol. The conversion of MVA to these polyprenyls in the presence of Isq is as efficient as its conversion to squalene and cholesterol in control cells. They conclude that the repressor of HMG-CoA reductase derived from MVA is a sterol - whatever might be the nature of that sterol - and not a nonsteroidal derivative of MVA metabolism. H4 cells exposed to Isq in lipid-depleted media die in 48-72 hr, but can be rescued by LDL, but not by free cholesterol or MVA. CHO cells are more resistant than H4 cells and succumb only after 8-9 days' exposure to Isq.
- Research Organization:
- Dept. of Agriculture, Albany, CA
- OSTI ID:
- 6023479
- Report Number(s):
- CONF-870644-
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 46:6; Conference: 78. annual meeting of the American Society of Biological Chemists conference, Philadelphia, PA, USA, 7 Jun 1987
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
CYCLASES
ENZYME ACTIVITY
SQUALENE
BIOLOGICAL EFFECTS
ACETATES
CARBON 14 COMPOUNDS
CELL CULTURES
CHO CELLS
COMPARATIVE EVALUATIONS
ENZYME INHIBITORS
HEPATOMAS
MEVALONIC ACID
OXIDOREDUCTASES
RATS
TRACER TECHNIQUES
TUMOR CELLS
ANIMAL CELLS
ANIMALS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
DISEASES
ENZYMES
HYDROCARBONS
HYDROXY ACIDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYASES
MAMMALS
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
POLYENES
RODENTS
TERPENES
VERTEBRATES
550201* - Biochemistry- Tracer Techniques