scholarly journals Transport of Cholesterol into Mitochondria Is Rate-limiting for Bile Acid Synthesis via the Alternative Pathway in Primary Rat Hepatocytes

2002 ◽  
Vol 277 (50) ◽  
pp. 48158-48164 ◽  
Author(s):  
William M. Pandak ◽  
Shunlin Ren ◽  
Dalila Marques ◽  
Elizabeth Hall ◽  
Kaye Redford ◽  
...  
Keyword(s):  
Bile Acid ◽  
Alternative Pathway ◽  
Rat Hepatocytes ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Primary Rat Hepatocytes ◽  
Rate Limiting

scholarly journals Cyclosporin A blocks bile acid synthesis in cultured hepatocytes by specific inhibition of chenodeoxycholic acid synthesis

1991 ◽  
Vol 275 (2) ◽  
pp. 501-505 ◽  
Author(s):  
H M Princen ◽  
P Meijer ◽  
B G Wolthers ◽  
R J Vonk ◽  
F Kuipers
Keyword(s):  
Bile Acid ◽  
Cyclosporin A ◽  
Bile Acids ◽  
Chenodeoxycholic Acid ◽  
Alternative Pathway ◽  
Rat Hepatocytes ◽  
Acid Synthesis ◽  
Liver Mitochondria ◽  
Bile Acid Synthesis ◽  
Rat Liver Mitochondria

Bile acid synthesis, determined by conversion of [4-14C]cholesterol into bile acids in rat and human hepatocytes and by measurement of mass production of bile acids in rat hepatocytes, was dose-dependently decreased by cyclosporin A, with 52% (rat) and 45% (human) inhibition of 10 microM. The decreased bile acid production in rat hepatocytes was due only to a fall in the synthesis of beta-muricholic and chenodeoxycholic acids (-64% at 10 microM-cyclosporin A), with no change in the formation of cholic acid. In isolated rat liver mitochondria, 26-hydroxylation of cholesterol was potently inhibited by the drug (concn. giving half-maximal inhibition = 4 microM). These results suggest that cyclosporin A blocks the alternative pathway in bile acid synthesis, which leads preferentially to the formation of chenodeoxycholic acid.

scholarly journals Flavonoids and saponins extracted from black bean (Phaseolus vulgaris L.) seed coats modulate lipid metabolism and biliary cholesterol secretion in C57BL/6 mice

2014 ◽  
Vol 112 (6) ◽  
pp. 886-899 ◽  
Author(s):  
Rocio A. Chavez-Santoscoy ◽  
Janet A. Gutierrez-Uribe ◽  
Omar Granados ◽  
Ivan Torre-Villalvazo ◽  
Sergio O. Serna-Saldivar ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Bile Acid ◽  
Phaseolus Vulgaris ◽  
Rat Hepatocytes ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bean Seed ◽  
Black Bean ◽  
Beneficial Effects ◽  
Seed Coats

Black bean (Phaseolus vulgaris L.) seed coats are a rich source of natural compounds with potential beneficial effects on human health. Beans exert hypolipidaemic activity; however, this effect has not been attributed to any particular component, and the underlying mechanisms of action and protein targets remain unknown. The aim of the present study was to identify and quantify primary saponins and flavonoids extracted from black bean seed coats, and to study their effects on lipid metabolism in primary rat hepatocytes and C57BL/6 mice. The methanol extract of black bean seed coats, characterised by a HPLC system with a UV–visible detector and an evaporative light-scattering detector and HPLC–time-of-flight/MS, contained quercetin 3-O-glucoside and soyasaponin Af as the primary flavonoid and saponin, respectively. The extract significantly reduced the expression of SREBP1c, FAS and HMGCR, and stimulated the expression of the reverse cholesterol transporters ABCG5/ABCG8 and CYP7A1 in the liver. In addition, there was an increase in the expression of hepatic PPAR-α. Consequently, there was a decrease in hepatic lipid depots and a significant increase in bile acid secretion. Furthermore, the ingestion of this extract modulated the proportion of lipids that was used as a substrate for energy generation. Thus, the results suggest that the extract of black bean seed coats may decrease hepatic lipogenesis and stimulate cholesterol excretion, in part, via bile acid synthesis.

scholarly journals Regulation of bile-acid synthesis. Role of sterol carrier protein2 in the biosynthesis of 7α-hydroxycholesterol

1985 ◽  
Vol 230 (1) ◽  
pp. 19-24 ◽  
Author(s):  
H Seltman ◽  
W Diven ◽  
M Rizk ◽  
B J Noland ◽  
R Chanderbhan ◽  
...  
Keyword(s):  
Bile Acid ◽  
Rat Liver ◽  
Liver Microsomes ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Gas Chromatography Mass Spectrometry ◽  
Rat Liver Microsomes ◽  
Rate Limiting Step ◽  
Rate Limiting

Sterol carrier protein2 (SCP2) is known to stimulate utilization of cholesterol in enzymic reactions in which cholesterol is the substrate. Substantial recent experimental evidence indicates that SCP2: activates enzymic conversion of intermediates between lanosterol and cholesterol; stimulates the microsomal conversion of cholesterol into cholesterol ester in rat liver; and enhances mitochondrial utilization of cholesterol for pregnenolone formation in the adrenals. The conversion of cholesterol into 7 α-hydroxycholesterol is the rate-limiting step in bile-acid synthesis. We therefore investigated the effect of SCP2 on this physiologically critical reaction by using a gas-chromatography-mass-spectrometry procedure that measures the mass of 7 α-hydroxycholesterol formed. The results show that SCP2 enhances 7 α-hydroxycholesterol formation by rat liver microsomes (microsomal fractions), utilizing either endogenous membrane cholesterol, cholesterol supplied exogenously in serum or in the form of cholesterol/phospholipid liposomes. Microsomes immunotitrated with anti-SCP2 antibody exhibited considerably less capacity to synthesize 7 α-hydroxycholesterol, which was restored to control levels on addition of purified SCP2. These data are consistent with the suggestion that SCP2 may be of physiological significance in the overall metabolism of cholesterol.

scholarly journals Dexamethasone regulates bile acid synthesis in monolayer cultures of rat hepatocytes by induction of cholesterol 7α-hydroxylase

1989 ◽  
Vol 262 (1) ◽  
pp. 341-348 ◽  
Author(s):  
H M Princen ◽  
P Meijer ◽  
B Hofstee
Keyword(s):  
Enzyme Activity ◽  
Bile Acid ◽  
Bile Acids ◽  
Steroid Hormones ◽  
Mrna Level ◽  
Rat Hepatocytes ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Hydroxylase Activity ◽  
Acid Pathway

To study the effect of steroid hormones on bile acid synthesis by cultured rat hepatocytes, cells were incubated with various amounts of these compounds during 72 h and conversion of [4-14C]cholesterol into bile acids was measured. Bile acid synthesis was stimulated in a dose-dependent way by glucocorticoids, but not by sex steroid hormones, pregnenolone or the mineralocorticoid aldosterone in concentrations up to 10 microM. Dexamethasone proved to be the most efficacious inducer, giving 3-fold and 7-fold increases in bile acid synthesis during the second and third 24 h incubation periods respectively, at a concentration of 50 nM. Mass production of bile acids as measured by g.l.c. during the second day of culture (28-52 h) was 2.2-fold enhanced by 1 microM-dexamethasone. No change in the ratio of bile acids produced was observed during this period in the presence of dexamethasone. Conversion of [4-14C]7 alpha-hydroxycholesterol, an intermediate of the bile acid pathway, to bile acids was not affected by dexamethasone. Measurement of cholesterol 7 alpha-hydroxylase activity in homogenates of hepatocytes, incubated with 1 microM-dexamethasone, showed 10-fold and 90-fold increases after 48 and 72 h respectively, as compared with control cells. As with bile acid synthesis from [14C]cholesterol, no change in enzyme activity was found in hepatocytes cultured in the presence of 10 microM steroid hormones other than glucocorticoids. Addition of inhibitors of protein and mRNA synthesis lowered bile acid production and cholesterol 7 alpha-hydroxylase activity and prevented the rise of both parameters with dexamethasone, suggesting regulation at the mRNA level. We conclude that glucocorticoids regulate bile acid synthesis in rat hepatocytes by induction of enzyme activity of cholesterol 7 alpha-hydroxylase.

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