Document Detail


Complement protein C1q recognizes enzymatically modified low-density lipoprotein through unesterified fatty acids generated by cholesterol esterase.
MedLine Citation:
PMID:  20166680     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Adrienn Biro; Wai Li Ling; G?rard J Arlaud
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochemistry     Volume:  49     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2010 Mar 
Date Detail:
Created Date:  2010-03-10     Completed Date:  2010-03-25     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2167-76     Citation Subset:  IM    
Affiliation:
Laboratoire d'Enzymologie Mol?culaire, Institut de Biologie Structurale Jean-Pierre Ebel, 41 rue Jules Horowitz, 38027 Grenoble Cedex 1, France.
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MeSH Terms
Descriptor/Qualifier:
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:
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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