| Annexin 2-caveolin 1 complex is a target of ezetimibe and regulates intestinal cholesterol transport. | |
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MedLine Citation:
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PMID: 14985510 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Modulation of cholesterol absorption in the intestine, the primary site of dietary cholesterol uptake in humans, can have profound clinical implications. We have undertaken a reverse genetic approach by disrupting putative cholesterol processing genes in zebrafish larvae by using morpholino (MO) antisense oligonucleotides. By using targeted MO injections and immunoprecipitation (IP) experiments coupled with mass spectrometry, we determined that annexin (ANX)2 complexes with caveolin (CAV)1 in the zebrafish and mouse intestine. The complex is heat stable and unaffected by SDS or reducing conditions. MO targeting of anx2b or cav1, which are both strongly expressed in the larval and adult zebrafish intestinal epithelium, prevents formation of the protein heterocomplex. Furthermore, anx2b MO injection prevents processing of a fluorescent cholesterol reporter and results in reduced sterol mass. Pharmacological treatment of mice with ezetimibe disrupts the heterocomplex in only hypercholesterolemic animals. These data suggest that ANX2 and CAV1 are components of an intestinal sterol transport complex. |
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Authors:
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Eric J Smart; Robert A De Rose; Steven A Farber |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S. Date: 2004-02-25 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 101 ISSN: 0027-8424 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2004 Mar |
Date Detail:
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Created Date: 2004-03-10 Completed Date: 2004-05-05 Revised Date: 2011-12-22 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 3450-5 Citation Subset: IM |
Affiliation:
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Department of Physiology, University of Kentucky, Lexington, KY 40536, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Annexin A2 / drug effects*, genetics, metabolism* Anticholesteremic Agents / pharmacology Azetidines / pharmacology* Base Sequence Caveolin 1 Caveolins / drug effects*, genetics, metabolism* Cholesterol / metabolism* Intestinal Absorption / drug effects*, physiology* Macromolecular Substances Mice Mice, Inbred C57BL Mice, Knockout Oligodeoxyribonucleotides, Antisense / genetics, pharmacology RNA, Messenger / genetics, metabolism Receptors, LDL / deficiency, genetics Zebrafish |
| Grant Support | |
ID/Acronym/Agency:
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DK60369/DK/NIDDK NIH HHS; GM63904/GM/NIGMS NIH HHS; HL58475/HL/NHLBI NIH HHS; HL62844/HL/NHLBI NIH HHS; HL64056/HL/NHLBI NIH HHS; R01 GM063904-01/GM/NIGMS NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Annexin A2; 0/Anticholesteremic Agents; 0/Azetidines; 0/Cav1 protein, mouse; 0/Caveolin 1; 0/Caveolins; 0/Macromolecular Substances; 0/Oligodeoxyribonucleotides, Antisense; 0/RNA, Messenger; 0/Receptors, LDL; 163222-33-1/ezetimibe; 57-88-5/Cholesterol |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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