| Targeting the ABCB4 gene to control cholesterol homeostasis. | |
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MedLine Citation:
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PMID: 21801087 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Introduction: Multidrug resistance 3 (MDR3) P-glycoprotein is a lipid floppase that is encoded by the ATP-binding cassette sub-family B member 4 (ABCB4) gene and plays a crucial role in proper bile formation by transporting phosphatidylcholine across the canalicular plasma membrane of the hepatocyte into bile. The relevance of this function is underscored by the severe pathology that develops in patients with ABCB4 deficiency. This deficiency leads to the destruction of hepatocytes and cholangiocytes by bile salts, because their cytolytic action is not reduced by formation of mixed micelles with phospholipid. Areas covered: Evidence that phospholipid secretion into bile is also essential for biliary cholesterol secretion as cholesterol dissolves much better in mixed micelles of bile salts and phospholipid than in pure bile salt micelles. As a consequence, net biliary cholesterol secretion depends on the amount of phospholipid secreted and hence, the expression of ABCB4 indirectly determines biliary cholesterol output. Expert opinion: It can be argued that upregulation of the ABCB4 gene expression may not only be beneficial for liver pathology in patients with partial ABCB4 deficiency, but also for the prevention of gallstone formation and optimal cholesterol disposition in a much larger population. |
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Authors:
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Ronald Pj Oude Elferink; Ulrich Beuers |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-7-30 |
Journal Detail:
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Title: Expert opinion on therapeutic targets Volume: - ISSN: 1744-7631 ISO Abbreviation: - Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-8-1 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101127833 Medline TA: Expert Opin Ther Targets Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Tytgat Institute for Liver and Intestinal Research , AMC S1-162, Meibergdreef 69-71, 1105 BK Amsterdam , The Netherlands +31 20 5663828 ; r.p.oude-elferink@amc.uva.nl. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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