Document Detail


Apolipoprotein modulation of streptococcal serum opacity factor activity against human plasma high-density lipoproteins.
MedLine Citation:
PMID:  19618959     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Human plasma HDL are the target of streptococcal serum opacity factor (SOF), a virulence factor that clouds human plasma. Recombinant (r) SOF transfers cholesteryl esters (CE) from approximately 400,000 HDL particles to a CE-rich microemulsion (CERM), forms a cholesterol-poor HDL-like particle (neo HDL), and releases lipid-free (LF) apo A-I. Whereas the rSOF reaction requires labile apo A-I, the modulation effects of other apos are not known. We compared the products and rates of the rSOF reaction against human HDL and HDL from mice overexpressing apos A-I and A-II. Kinetic studies showed that the reactivity of various HDL species is apo-specific. LpA-I reacts faster than LpA-I/A-II. Adding apos A-I and A-II inhibited the SOF reaction, an effect that was more profound for apo A-II. The rate of SOF-mediated CERM formation was slower against HDL from mice expressing human apos A-I and A-II than against WT mice HDL and slowest against HDL from apo A-II overexpressing mice. The lower reactivity of SOF against HDL containing human apos is due to the higher hydropathy of human apo A-I, particularly its C-terminus relative to mouse apo A-I, and the higher lipophilicity of human apo A-II. The SOF-catalyzed reaction is the first to target HDL rather than its transporters and receptors in a way that enhances reverse cholesterol transport (RCT). Thus, effects of apos on the SOF reaction are highly relevant. Our studies show that the "humanized" apo A-I-expressing mouse is a good animal model for studies of rSOF effects on RCT in vivo.
Authors:
Corina Rosales; Baiba K Gillard; Harry S Courtney; Francisco Blanco-Vaca; Henry J Pownall
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Biochemistry     Volume:  48     ISSN:  1520-4995     ISO Abbreviation:  Biochemistry     Publication Date:  2009 Aug 
Date Detail:
Created Date:  2009-08-18     Completed Date:  2009-09-25     Revised Date:  2012-05-04    
Medline Journal Info:
Nlm Unique ID:  0370623     Medline TA:  Biochemistry     Country:  United States    
Other Details:
Languages:  eng     Pagination:  8070-6     Citation Subset:  IM    
Affiliation:
Section of Atherosclerosis and Vascular Medicine, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apolipoprotein A-I / biosynthesis,  genetics,  metabolism,  physiology*
Apolipoprotein A-II / biosynthesis,  genetics,  physiology*,  secretion
Catalysis
Cholesterol Ester Transfer Proteins / antagonists & inhibitors,  chemistry,  physiology
Cholesterol Esters / metabolism
Emulsions
Humans
Lipoproteins, HDL / antagonists & inhibitors*,  blood
Mice
Mice, Transgenic
Nephelometry and Turbidimetry
Peptide Fragments / biosynthesis,  genetics,  physiology
Peptide Hydrolases / blood*,  genetics,  physiology
Protein Binding
Recombinant Proteins / blood,  chemistry,  genetics
Streptococcus pyogenes / chemistry,  physiology*
Grant Support
ID/Acronym/Agency:
HL 30914/HL/NHLBI NIH HHS; HL056865/HL/NHLBI NIH HHS; R01 HL030914-22S1/HL/NHLBI NIH HHS; R01 HL056865/HL/NHLBI NIH HHS; R01 HL056865-09A2/HL/NHLBI NIH HHS
Chemical
Reg. No./Substance:
0/APOA1 protein, human; 0/APOA2 protein, human; 0/Apolipoprotein A-I; 0/Apolipoprotein A-II; 0/Cholesterol Ester Transfer Proteins; 0/Cholesterol Esters; 0/Emulsions; 0/Lipoproteins, HDL; 0/Peptide Fragments; 0/Recombinant Proteins; 0/opacity factor; EC 3.4.-/Peptide Hydrolases

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