Effects of 2,3-iminosqualene in cultured cells

Conference · Fri May 01 04:00:00 EDT 1987 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:6023479

Popjak, G; Meenan, A; Nes, W D

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-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 46:6
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETATES
ANIMAL CELLS
ANIMALS
BIOLOGICAL EFFECTS
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CELL CULTURES
CHO CELLS
COMPARATIVE EVALUATIONS
CYCLASES
DISEASES
ENZYME ACTIVITY
ENZYME INHIBITORS
ENZYMES
HEPATOMAS
HYDROCARBONS
HYDROXY ACIDS
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LYASES
MAMMALS
MEVALONIC ACID
NEOPLASMS
ORGANIC ACIDS
ORGANIC COMPOUNDS
OXIDOREDUCTASES
POLYENES
RATS
RODENTS
SQUALENE
TERPENES
TRACER TECHNIQUES
TUMOR CELLS
VERTEBRATES