Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and ABCG8

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Biliary cholesterol secretion by the twinned sterol half-transporters ABCG5 and ABCG8.

The long wait for a cellular and functional definition of canalicular transporters for biliary cholesterol appears to be over. Articles in this issue of the JCI provide a fascinating account of the cellular itinerary of two murine ATP-binding cassette (ABC) halftransporters from the ribosome to the hepatocyte apical membranes (1) and show that the corresponding human genes, when overexpressed i...

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Polymorphisms in ABCG5 and ABCG8 transporters and plasma cholesterol levels.

ABCG5 and ABCG8 transporters play an important role in the absorption and excretion of sterols. Missence polymorphisms (Gln604Glu in the ABCG5 and Asp19His, Tyr54Cys, Thr400Lys, and Ala632Val in the ABCG8) in these genes have been described. In 131 males and 154 females whose dietary composition markedly changed and lipid parameters decreased over an 8-year follow-up study (total cholesterol de...

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Overexpression of ABCG5 and ABCG8 promotes biliary cholesterol secretion and reduces fractional absorption of dietary cholesterol.

Two ATP-binding cassette (ABC) transporters, ABCG5 and ABCG8, have been proposed to limit sterol absorption and to promote biliary sterol excretion in humans. To test this hypothesis, a P1 clone containing the human ABCG5 and ABCG8 genes was used to generate transgenic mice. The transgenes were expressed primarily in the liver and small intestine, mirroring the expression pattern of the endogen...

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Disruption of Abcg5 and Abcg8 in mice reveals their crucial role in biliary cholesterol secretion.

Cholesterol and other sterols exit the body primarily by secretion into bile. In patients with sitosterolemia, mutations in either of two ATP-binding cassette (ABC) half-transporters, ABCG5 or ABCG8, lead to reduced secretion of sterols into bile, implicating these transporters in this process. To elucidate the roles of ABCG5 and ABCG8 in the trafficking of sterols, we disrupted Abcg5 and Abcg8...

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ABCG5/ABCG8-independent biliary cholesterol excretion in lactating rats.

Lactation is associated with increased expression of bile acid transporters and an increased size and hydrophobicity of the bile acid pool in rats. ATP-binding cassette (ABC) transporters multidrug resistance protein 2 (Mdr2), Abcb11 [bile salt export pump (Bsep)], and Abcg5/Abcg8 heterodimers are essential for the biliary secretion of phospholipids, bile acids, and cholesterol, respectively. W...

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ژورنال

عنوان ژورنال: Journal of Clinical Investigation

سال: 2002

ISSN: 0021-9738

DOI: 10.1172/jci0216548