Receptor-mediated uptake of low density lipoprotein stimulates bile acid synthesis by cultured rat hepatocytes
- Univ. of Colorado Health Sciences Center, Denver (USA)
The cellular mechanisms responsible for the lipoprotein-mediated stimulation of bile acid synthesis in cultured rat hepatocytes were investigated. Adding 280 micrograms/ml of cholesterol in the form of human or rat low density lipoprotein (LDL) to the culture medium increased bile acid synthesis by 1.8- and 1.6-fold, respectively. As a result of the uptake of LDL, the synthesis of (14C)cholesterol from (2-14C)acetate was decreased and cellular cholesteryl ester mass was increased. Further studies demonstrated that rat apoE-free LDL and apoE-rich high density lipoprotein (HDL) both stimulated bile acid synthesis 1.5-fold, as well as inhibited the formation of (14C)cholesterol from (2-14C)acetate. Reductive methylation of LDL blocked the inhibition of cholesterol synthesis, as well as the stimulation of bile acid synthesis, suggesting that these processes require receptor-mediated uptake. To identify the receptors responsible, competitive binding studies using 125I-labeled apoE-free LDL and 125I-labeled apoE-rich HDL were performed. Both apoE-free LDL and apoE-rich HDL displayed an equal ability to compete for binding of the other, suggesting that a receptor or a group of receptors that recognizes both apolipoproteins is involved. Additional studies show that hepatocytes from cholestyramine-treated rats displayed 2.2- and 3.4-fold increases in the binding of apoE-free LDL and apoE-rich HDL, respectively. These data show for the first time that receptor-mediated uptake of LDL by the liver is intimately linked to processes activating bile acid synthesis.
- OSTI ID:
- 7191900
- Journal Information:
- Journal of Lipid Research; (USA), Journal Name: Journal of Lipid Research; (USA) Vol. 30:12; ISSN JLPRA; ISSN 0022-2275
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
59 BASIC BIOLOGICAL SCIENCES
ACETATES
ANIMALS
BETA DECAY RADIOISOTOPES
BILE ACIDS
BIOCHEMICAL REACTION KINETICS
BIOSYNTHESIS
BODY
CARBON 14 COMPOUNDS
CARBOXYLIC ACID SALTS
CARBOXYLIC ACIDS
CHEMICAL REACTIONS
CHOLESTEROL
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LABELLED COMPOUNDS
LIPIDS
LIPOPROTEINS
LIVER
MAMMALS
MAN
MEMBRANE PROTEINS
METHYLATION
NUCLEI
ODD-EVEN NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANS
PRIMATES
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
RECEPTORS
RODENTS
STEROIDS
STEROLS
SYNTHESIS
TRACER TECHNIQUES
UPTAKE
VERTEBRATES