| VLDL lipolysis products increase VLDL fluidity and convert apolipoprotein E4 into a more expanded conformation. | |
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MedLine Citation:
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PMID: 19965582 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Our previous work indicated that apolipoprotein (apo) E4 assumes a more expanded conformation in the postprandial period. The postprandial state is characterized by increased VLDL lipolysis. In this article, we tested the hypothesis that VLDL lipolysis products increase VLDL particle fluidity, which mediates expansion of apoE4 on the VLDL particle. Plasma from healthy subjects was collected before and after a moderately high-fat meal and incubated with nitroxyl-spin labeled apoE. ApoE conformation was examined by electron paramagnetic resonance spectroscopy using targeted spin probes on cysteines introduced in the N-terminal (S76C) and C-terminal (A241C) domains. Further, we synthesized a novel nitroxyl spin-labeled cholesterol analog, which gave insight into lipoprotein particle fluidity. Our data revealed that the order of lipoprotein fluidity was HDL approximately LDL<VLDL<VLDL+lipoprotein lipase. Moreover, the conformation of apoE4 depended on the lipoprotein fraction: VLDL-associated apoE4 had a more linear conformation than apoE4 associated with LDL or HDL. Further, by changing VLDL fluidity, VLDL lipolysis products significantly altered apoE4 into a more expanded conformation. Our studies indicate that after every meal, VLDL fluidity is increased causing apoE4 associated with VLDL to assume a more expanded conformation, potentially enhancing the pathogenicity of apoE4 in vascular tissue. |
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Authors:
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Sarada D Tetali; Madhu S Budamagunta; Catalina Simion; Laura J den Hartigh; Tamás Kálai; Kálmán Hideg; Danny M Hatters; Karl H Weisgraber; John C Voss; John C Rutledge |
Publication Detail:
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Type: Clinical Trial; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2009-12-03 |
Journal Detail:
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Title: Journal of lipid research Volume: 51 ISSN: 0022-2275 ISO Abbreviation: J. Lipid Res. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-12 Completed Date: 2010-08-17 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: United States |
Other Details:
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Languages: eng Pagination: 1273-83 Citation Subset: IM |
Affiliation:
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Department of Plant Sciences, School of Life Sciences, University of Hyderabad, Hyderabad 500 046, India. sdtsl@uohyd.ernet.in |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apolipoprotein E3
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chemistry Apolipoprotein E4 / blood, chemistry*, metabolism* Electron Spin Resonance Spectroscopy Humans Lipolysis* Lipoproteins, HDL / metabolism Lipoproteins, VLDL / metabolism* Models, Molecular Peptide Fragments / chemistry, metabolism Postprandial Period Protein Structure, Tertiary Vascular Diseases / metabolism |
| Grant Support | |
ID/Acronym/Agency:
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C06 RR-12088-01/RR/NCRR NIH HHS; HL-55667/HL/NHLBI NIH HHS; HL-HL71488/HL/NHLBI NIH HHS; R01 AG 028793/AG/NIA NIH HHS; R01 AG029246/AG/NIA NIH HHS; R01 AG029246-01A1/AG/NIA NIH HHS; R01 AG029246-05/AG/NIA NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Apolipoprotein E3; 0/Apolipoprotein E4; 0/Lipoproteins, HDL; 0/Lipoproteins, VLDL; 0/Peptide Fragments |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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