| Complement protein C1q recognizes enzymatically modified low-density lipoprotein through unesterified fatty acids generated by cholesterol esterase. | |
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MedLine Citation:
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PMID: 20166680 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We previously reported that enzymatically modified low-density lipoprotein (E-LDL) particles obtained by LDL treatment with trypsin and then cholesterol esterase are recognized by C1q and activate the C1 complex of complement. The objective of this study was to identify the E-LDL component(s) recognized by C1q. In addition to trypsin, plasmin, thrombin, tryptase, and matrix metalloprotease-2 each yielded E-LDL particles with high C1-activating efficiency, and the C1 activation extent was strictly dependent on cholesterol esterase treatment in all cases. When incorporated into vesicles, the lipid fraction of E-LDL, but not of native LDL, triggered C1 activation, and activation correlated with the amount of unesterified cholesterol generated by cholesterol esterase. Whereas treatment of E-LDL particles with human serum albumin reduced their fatty acid content, both cholesterol and unesterified fatty acids were decreased by methyl-beta-cyclodextrin, both treatments resulting in dose-dependent inhibition of the C1-activating ability of the particles. Incorporation of linoleic acid into phosphatidylcholine-containing model vesicles enabled them to interact with the C1q globular domain and to trigger C1 activation, and cholesterol enhanced both processes by facilitating incorporation of the fatty acid into the vesicles. Direct evidence that C1q binds E-LDL through its globular domains was obtained by electron microscopy. This study demonstrates that C1 binding to E-LDL particles involves recognition by the C1q globular domain of the unesterified fatty acids generated by cholesterol esterase. The potential implications of these findings in atherogenesis are discussed. |
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Authors:
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Adrienn Biro; Wai Li Ling; G?rard J Arlaud |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Biochemistry Volume: 49 ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2010 Mar |
Date Detail:
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Created Date: 2010-03-10 Completed Date: 2010-03-25 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
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Languages: eng Pagination: 2167-76 Citation Subset: IM |
Affiliation:
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Laboratoire d'Enzymologie Mol?culaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Candida / enzymology Cattle Complement C1q / chemistry, metabolism* Esterification Fatty Acids / chemistry, metabolism* Humans Linoleic Acid / metabolism Lipoproteins, LDL / metabolism* Microscopy, Electron Peptide Hydrolases / metabolism Protein Binding Protein Structure, Tertiary Serum Albumin / pharmacology Sterol Esterase / metabolism* beta-Cyclodextrins / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Fatty Acids; 0/Lipoproteins, LDL; 0/Serum Albumin; 0/beta-Cyclodextrins; 0/methyl-beta-cyclodextrin; 2197-37-7/Linoleic Acid; 80295-33-6/Complement C1q; EC 3.1.1.13/Sterol Esterase; EC 3.4.-/Peptide Hydrolases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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