[Probucol and alpha-tocopherol stimulate the synthesis of bile acids in cultured rabbit hepatocytes].
Primary cultures of rabbit hepatocytes were used to examine the effect of probucol and alpha-tocopherol on cholesterol and bile acid metabolism. After 24-hour preincubation of cells with 100 microM probucol, the cholesterol and cholesteryl ester content increased--by 30% and 50%, respectively. This was accompanied by decreasing incorporation of [14C]acetate into cholesterol (down to 25-35%). At the same time, alpha-tocopherol had no effect on cholesterol accumulation in hepatocytes, while cholesterol synthesis was stimulated by 30-50%. Addition of 100 microM probucol or alpha-tocopherol to a culture medium containing 10% fetal calf serum and [14C]cholesterol caused a significant (30-40%) stimulation of bile acid synthesis. Stimulation by probucol was dependent on the presence of exogenous plasma or HDL2 cholesterol, while alpha-tocopherol enhanced this process in a cholesterol-free medium. Stimulation (40%) of bile acid secretion by probucol in the presence of physiological concentrations of apo E-free HDL2 was found. Study of receptor-mediated uptake of HDL2 revealed that: (i) probucol stimulated apo E secretion; (ii) HDL2 isolated from a medium of probucol-treated cells contained 2-3 times more apo E than the particles preincubated with cells without the drug; (iii) apo E-enriched HDL2 particles were incorporated into cultured human skin fibroblasts 1.5-3.0 times more effectively than apo E depleted HDL2; (iv) monoclonal antibody against the LDL-receptor binding domain of apo E effectively (by 40%) inhibited the apo E-enriched HDL2 uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Lakeev
Iu V
IuV
Kosykh
V A
VA
Kosenkov
E I
EI
Tsibul'skiĭ
V P
VP
Tikhomirov
O Iu
OIu
Antonov
I A
IA
Repin
V S
VS
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000378:metabolism; D002478:Cells, Cultured; D002784:Cholesterol / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011341:Probucol / Q000494:pharmacology*; D011817:Rabbits; D014810:Vitamin E / Q000494:pharmacology*
D001647:Bile Acids and Salts; D008075:Lipoproteins, HDL; D014810:Vitamin E; D002784:Cholesterol; D011341:Probucol
Probukol i alpha-tokoferol stimuliruiut sintez zhelchnykh kislot v kul'tiviruemykh gepatotsitakh krolika.