Research article summary (published 29 Sep 2009):

Scavenger receptor class B type I mediates biliary cholesterol secretion independent of ATP-binding cassette transporter g5/g8 in mice.

Full Abstract

Scavenger receptor class B type I (SR-BI) mediates selective uptake of cholesterol from high-density lipoprotein (HDL) particles by the liver and influences biliary cholesterol secretion. However, it is not clear, if this effect is direct or indirect. The aim of this study was to determine the impact of SR-BI on biliary cholesterol secretion, especially in a functional context with ATP-binding cassette transporter g5 (Abcg5)/Abcg8 and Abcb4. SR-BI was overexpressed by means of adenovirus (AdSR-BI) in livers of wild-type, liver X receptor-null (Lxr(-/-)), Abcg5(-/-), and Abcb4(-/-) mice. Consistent with previous reports, AdSR-BI decreased plasma HDL cholesterol levels in all models (P < 0.001). Hepatic cholesterol content increased (at least P < 0.05), whereas expression of sterol regulatory element binding protein 2 target genes was decreased (at least P < 0.05,) and established Lxr target genes were unaltered. Biliary cholesterol secretion was increased by AdSR-BI in wild-type as well as in Lxr(-/-) and Abcg5(-/-) mice, and considerably less in Abcb4(-/-) mice (each P < 0.001), independent of bile acid and phospholipid secretion. Immunogold electron microscopy and western blot showed a substantial increase of SR-BI protein localized to basolateral and canalicular membranes in response to SR-BI overexpression. Subcellular fractionation revealed a significantly higher cholesterol content of canalicular membranes (P < 0.001) upon SR-BI overexpression. Inhibition of microtubule function did not affect SR-BI-mediated biliary cholesterol secretion, indicating that transcytosis pathways are not involved. CONCLUSION: Our data indicate that SR-BI mediates biliary cholesterol secretion independent of Abcg5, yet largely depends on Abcb4-mediated phospholipid secretion and mixed micelles as acceptors in bile. SR-BI-mediated biliary cholesterol secretion has a high capacity, can compensate for the absence of Abcg5, and does not require transcytosis pathways.

Author information

Author/s: Wiersma, Harmen (H); Gatti, Alberto (A); Nijstad, Niels (N); Oude Elferink, Ronald P J (RP); Kuipers, Folkert (F); Tietge, Uwe J F (UJ);

Affiliation: Department of Pediatrics, Center for Liver, Digestive and Metabolic Diseases, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Hepatology (Baltimore, Md.) (Hepatology), published in United States. (Language: eng)

Reference: 2009-Oct; vol 50 (issue 4) : pp 1263-72

Dates: Created 2009/10/05; Completed 2009/10/20;

PMID: 19637290, status: MEDLINE (last retrieval date: 10/20/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

ATP-Binding Cassette Transporters - genetics; metabolism Animals Cholesterol - metabolism Cholesterol, HDL - blood DNA-Binding Proteins - genetics; metabolism Lipoproteins - genetics; metabolism Liver - metabolism

Liver - metabolism Mice Mice, Knockout Microtubules - physiology Models, Animal Receptors, Cytoplasmic and Nuclear - genetics; metabolism Scavenger Receptors, Class B - metabolism

Associated Chemicals: ABCG5 protein, mouse (0) ; ABCG8 protein, mouse (0) ; ATP-Binding Cassette Transporters (0) ; Abcg4 protein, mouse (0) ; Cholesterol, HDL (0) ; DNA-Binding Proteins (0) ; Lipoproteins (0) ; Receptors, Cytoplasmic and Nuclear (0) ; Scarb1 protein, mouse (0) ; Scavenger Receptors, Class B (0) ; liver X receptor (0) ; Cholesterol (57-88-5)

Related articles

These are the highest related articles currently in the database:

• SR-BI inhibits ABCG1-stimulated net cholesterol efflux from cells to plasma HDL. 22 Oct 2007
• Chronic contamination with 137cesium in rat: effect on liver cholesterol metabolism. 30 Oct 2006
• Abcg5/Abcg8-independent pathways contribute to hepatobiliary cholesterol secretion in mice. 11 Apr 2006
• Sitosterolemia: a gateway to new knowledge about cholesterol metabolism. 30 Dec 2002
• Cellular SR-BI and ABCA1-mediated cholesterol efflux are gender-specific in healthy subjects. 3 Dec 2007
• Expression of ABCG5 and ABCG8 is required for regulation of biliary cholesterol secretion. 14 Dec 2004
• Studies on the cholesterol-free mouse: strong activation of LXR-regulated hepatic genes when replacing cholesterol with desmosterol. 28 Aug 2007
• Effect of cholesterol, cholic acid and cholestyramine administration on the intestinal mRNA expressions related to cholesterol and bile acid metabolism in the rat. 11 May 2007
• Genetic disorders associated with ATP binding cassette cholesterol transporters. 30 Aug 2002
• [Liver X receptors mediate cholesterol efflux in mouse glomerular mesangial cells] 16 Jun 2006

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.