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Prevention of LDL-suppression of HMG-CoA reductase (HMGR) activity by progesterone (PG): evidence for cytochrome P-450 involvement

Conference · · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)
OSTI ID:5904895
; ; ;
Incubation of rat intestinal epithelial cells (IEC-6) with PG has been reported by us to prevent the suppression of HMGR activity by LDL. In the present study, addition of LDL and PG to IEC-6 cells resulted in a 2 fold increase in cellular free cholesterol (CH) in 24 h, while HMGR activity remained elevated. PG did not affect the internalization and degradation of (/sup 125/I) LDL nor the accumulation of free (/sup 3/H) CH in cells incubated with (/sup 3/H-cholesteryl linoleate)-LDL. Also, PG did not affect the intracellular transport of LDL-derived (/sup 3/H) CH to the plasma membrane nor the efflux of the (/sup 3/H) CH into medium containing human high density lipoprotein. Addition of LDL to cells, in which the cellular CH was radiolabeled from (/sup 3/H) acetate, resulted in an increased formation of radiolabeled oxysterols, detected by HPLC, and a corresponding decrease in HMGR activity. PG attenuated both the LDL-induced formation of oxysterols and suppression of HMGR activity. PG inhibited cytochrome P-450 dependent oxidation of benzphetamine, aminopyrine and aniline by liver microsomes from phenobarbitol treated rats. These results suggest PG may prevent LDL suppression of HMGR activity in IEC-6 cells by inhibiting cytochrome P-450 dependent formation of regulatory oxysterols.
Research Organization:
Univ. of Cincinnati, OH
OSTI ID:
5904895
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

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Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACETATES
ANIMAL CELLS
ANIMAL TISSUES
ANIMALS
BETA DECAY RADIOISOTOPES
BIOLOGICAL FUNCTIONS
BIOSYNTHESIS
BODY
CARBOXYLIC ACID SALTS
CELL CONSTITUENTS
CHOLESTEROL
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
ENZYME ACTIVITY
ENZYMES
EPITHELIUM
FUNCTIONS
GASTROINTESTINAL TRACT
GLANDS
HORMONES
HYDROXY COMPOUNDS
INHIBITION
INTERMEDIATE MASS NUCLEI
INTESTINES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KETONES
LABELLED COMPOUNDS
LIVER
MAMMALS
MEMBRANE TRANSPORT
MICROSOMES
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
OXIDOREDUCTASES
PREGNANES
PROGESTERONE
RADIOISOTOPES
RATS
RODENTS
STEROID HORMONES
STEROIDS
STEROLS
SYNTHESIS
TISSUES
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES