Relation between hepatic expression of ATP-binding cassette transporters G5 and G8 and biliary cholesterol secretion in mice

Kosters, Astrid; Frijters, Raoul; Schaap, Frank G.; Vink, Erik P. de; Plösch, Torsten; Ottenhoff, Roelof; Jirsa, M; Cuyper, Iris M. De; Kuipers, Folkert; Groen, Albert K.

doi:10.1016/s0168-8278(03)00093-x

Cited by 79 publications

(78 citation statements)

References 32 publications

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“…In fact, our recent observation that cholesterol secretion is unaffected in Abca1 null mice lacking HDL [35] strongly argues against a regulatory role of cholesterol delivery. A concise overview of various models of cholesterol hypo-and hypersecretion indicated that, at least in mice, biliary cholesterol secretion strongly correlates with hepatic Abcg5/Abcg8 expression [21]. Accordingly, we propose that impaired hepatic expression of both half-transporters underlies impaired cholesterol secretion in diabetic rats.…”

Section: Discussionmentioning

confidence: 78%

“…Membranes were blocked in TTBS and subsequently incubated for 1 h at room temperature with primary antibodies, raised in rabbits against amino acids 256-392 of murine Abcg5 [21], diluted 1:1000 in blocking buffer. Membranes were washed thrice in TTBS and incubated with horseradish peroxidase-conjugated V. W. Bloks et al: Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated 105 secretion of cholesterol into bile is coupled to that of phospholipids in a process that is, in part, controlled by bile salt secretion [6].…”

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confidence: 99%

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Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Bloks¹,

Waarde²,

Verkade³

et al. 2004

Diabetologia

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Aim/hypothesis. Type I diabetes is associated with altered hepatic bile formation and increased intestinal cholesterol absorption. The aim of this study was to evaluate whether altered expression of the ATP-Binding Cassette half-transporters Abcg5 and Abcg8, recently implicated in control of both hepatobiliary cholesterol secretion and intestinal cholesterol absorption, contributes to changed cholesterol metabolism in experimental diabetes. Methods. mRNA and protein expression of Abcg5 and Abcg8 were determined in the liver and intestine of rats with streptozotozin-induced diabetes and related to relevant metabolic parameters in plasma, liver and bile. Results. Hepatic mRNA expression of both Abcg5 (−76%) and Abcg8 (−71%) was reduced in diabetic rats when compared to control rats. In spite of increased HDL cholesterol, considered a major source of biliary cholesterol, secretion of the sterol into bile relative to that of bile salts was reduced by 65% in diabetic animals. Intestinal mRNA expression of Abcg5 (−47%) and Abcg8 (−43%) as well as Abcg5 protein contents were also reduced in insulin-deficient animals. This was accompanied by a three-to four-fold increase in plasma β-sitosterol and campesterol concentrations and by a doubling of the calculated apparent cholesterol absorption. These effects partially normalized upon insulin supplementation. Conclusion/interpretation. Our data indicate that effects of insulin-deficiency on bile composition and cholesterol absorption in rats are, at least partly, attributable to changes in hepatic and intestinal Abcg5 and Abcg8 expression. [Diabetologia (2004) Type I diabetes mellitus is associated with specific changes in cholesterol metabolism in humans [1] and in experimental animals [2,3], including increased concentrations of plasma cholesterol, enhanced conversion of cholesterol into bile salts and an enhanced intestinal cholesterol absorption. The hepatobiliary pathway is of crucial importance for the maintenance of cholesterol homeostasis [4]. Bile salts that are secreted by the liver into the intestinal lumen are required for intestinal absorption of dietary cholesterol. The majority of bile salts is subsequently reabsorbed from the intestine and returns to the liver for re-secretion into the bile. The relatively small fraction of bile salts that escapes intestinal absorption is compensated for by de novo synthesis from cholesterol in the liver. Secondly, bile contains considerable amounts of free cholesterol. Since only a part of biliary cholesterol is reabsorbed from the intestine [5], the biliary pathway contributes to a major extent to cholesterol turnover. It is well-established that

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Section: Discussionmentioning

confidence: 78%

mentioning

confidence: 99%

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Bloks¹,

Waarde²,

Verkade³

et al. 2004

Diabetologia

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“…Membranes were incubated with anti-ABCG5 primary antibody. 30 Immune complexes were visualized using horseradish peroxidase-conjugated goat anti-rabbit (DAKO, Heverlee, Belgium) and SuperSignal West Dura substrate (ThermoScientific, Rockford, IL, USA).…”

Section: Western Blotting For Abcg5 Protein Expressionmentioning

confidence: 99%

Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

et al. 2017

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“…Up to 1 lgram protein was fractionated by 10% SDS-PAGE, blotted overnight, blocked in phosphate-buffered saline (PBS)/4% milk powder/ 0.05% Tween-20, and incubated with anti-Abcg5 [21]. Immune complexes were visualized with horseradish peroxidase-conjugated immunoglobulins and detected using enhanced chemiluminescence (Amersham, Buckinghamshire, UK).…”

Section: Plasma Membrane Detection Of Abcg5mentioning

confidence: 99%

The sterol transporting heterodimer ABCG5/ABCG8 requires bile salts to mediate cholesterol efflux

et al. 2007

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The ATP binding cassette transporters ABCG5 and ABCG8 are indispensable for hepatobiliary cholesterol transport. In this study, we investigated the specificity of the heterodimer for cholesterol acceptors. Dog gallbladder epithelial cells were mono-or double-transfected with lentiviral mouse Abcg5 and Abcg8 vectors. Double-transfected cells showed increased efflux to different bile salt (BS) species, while mono-transfected cells did not show enhanced efflux. The efflux was initiated at micellar concentrations and addition of phosphatidylcholine increased efflux. Cholesterol secretion was highly BS dependent, whereas other cholesterol acceptors such as ApoAI, HDL or methyl-b-cyclodextrin did not elicit Abcg5/g8 dependent cholesterol secretion.

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Relation between hepatic expression of ATP-binding cassette transporters G5 and G8 and biliary cholesterol secretion in mice

Cited by 79 publications

References 32 publications

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Down-regulation of hepatic and intestinal Abcg5 and Abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

Intestinal Farnesoid X Receptor Controls Transintestinal Cholesterol Excretion in Mice

The sterol transporting heterodimer ABCG5/ABCG8 requires bile salts to mediate cholesterol efflux

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