| Alteration of negatively charged residues in the 89 to 99 domain of ApoA-I affects lipid homeostasis and the maturation of HDL. | |
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MedLine Citation:
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PMID: 21504968 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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The objective of the present study was to investigate the role of positively and negatively charged amino acids within the 89-99 region of apolipoprotein A-I (apoA-I), that are highly conserved in mammals, on plasma lipid homeostasis and the biogenesis of HDL. We have shown previously that deletion of the 89-99 region of apoA-I increased plasma cholesterol and phospholipids but did not affect plasma triglycerides.Functional studies using adenovirus-mediated gene transfer of two apoA-I mutants in apoA-I deficient mice showed that apoA-I[D89A/E91A/E92A] increased plasma cholesterol and caused severe hypertriglyceridemia. HDL levels were reduced and approximately 40% of the apoA-I was distributed in VLDL/IDL. The HDL consisted of mostly spherical and few discoidal particles and contained preβ1 and α4-HDL subpopulations. The lipid, lipoprotein and HDL profiles generated by the apoA-I[K94A/K96A] mutant were similar to those of wild type apoA-I. Co-expression of apoA-I[D89A/E91A/E92A] and human lipoprotein lipase abolished hypertriglyceridemia, restored in part the α1,2,3,4 HDL subpopulations, redistributed apoA-I in the HDL2/HDL3 regions, but did not prevent the formation of discoidal HDL particles. Physicochemical studies showed that the apoA-I[D89A/E91A/E92A] mutant had reduced α-helical content and effective enthalpy of thermal denaturation, increased exposure of hydrophobic surfaces and increased affinity for triglyceride-rich emulsions. We conclude that residues D89, E91 and E92 of apoA-I are important for plasma cholesterol and triglyceride homeostasis as well as for the maturation of HDL. |
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Authors:
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Andreas K Kateifides; Irina N Gorshkova; Adelina Duka; Angeliki Chroni; Dimitris Kardassis; Vassilis I Zannis |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-4-19 |
Journal Detail:
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Title: Journal of lipid research Volume: - ISSN: 0022-2275 ISO Abbreviation: - Publication Date: 2011 Apr |
Date Detail:
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Created Date: 2011-4-20 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0376606 Medline TA: J Lipid Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Boston University School of Medicine, United States; |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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