| Streptococcal serum opacity factor increases the rate of hepatocyte uptake of human plasma high-density lipoprotein cholesterol. | |
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MedLine Citation:
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PMID: 20879789 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Serum opacity factor (SOF), a virulence determinant of Streptococcus pyogenes, converts plasma high-density lipoproteins (HDL) to three distinct species: lipid-free apolipoprotein (apo) A-I, neo HDL, a small discoidal HDL-like particle, and a large cholesteryl ester-rich microemulsion (CERM) that contains the cholesterol esters (CE) of up to ∼400000 HDL particles and apo E as its major protein. Similar SOF reaction products are obtained with HDL, total plasma lipoproteins, and whole plasma. We hypothesized that hepatic uptake of CERM-CE via multiple apo E-dependent receptors would be faster than that of HDL-CE. We tested our hypothesis using human hepatoma cells and lipoprotein receptor-specific Chinese hamster ovary (CHO) cells. The uptake of [(3)H]CE by HepG2 and Huh7 cells from HDL after SOF treatment, which transfers >90% of HDL-CE to CERM, was 2.4 and 4.5 times faster, respectively, than from control HDL. CERM-[(3)H]CE uptake was inhibited by LDL and HDL, suggestive of uptake by both the LDL receptor (LDL-R) and scavenger receptor class B type I (SR-BI). Studies in CHO cells specifically expressing LDL-R and SR-BI confirmed CERM-[(3)H]CE uptake by both receptors. RAP and heparin inhibit CERM-[(3)H]CE but not HDL-[(3)H]CE uptake, thereby implicating LRP-1 and cell surface proteoglycans in this process. These data demonstrate that SOF treatment of HDL increases the rate of CE uptake via multiple hepatic apo E receptors. In so doing, SOF might increase the level of hepatic disposal of plasma cholesterol in a way that is therapeutically useful. |
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Authors:
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Baiba K Gillard; Corina Rosales; Biju K Pillai; Hu Yu Lin; Harry S Courtney; Henry J Pownall |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S. Date: 2010-10-25 |
Journal Detail:
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Title: Biochemistry Volume: 49 ISSN: 1520-4995 ISO Abbreviation: Biochemistry Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-09 Completed Date: 2010-12-22 Revised Date: 2011-11-21 |
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: 9866-73 Citation Subset: IM |
Affiliation:
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Section of Cardiovascular Research, Department of Medicine, Baylor College of Medicine, Houston, Texas 77030, United States. baibag@bcm.tmc.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Boron Compounds / metabolism CHO Cells / metabolism Cell Culture Techniques Cholesterol Esters / metabolism Cholesterol, HDL / drug effects, metabolism* Cricetinae Cricetulus Hepatocytes / cytology, drug effects, metabolism* Humans Kinetics Liver / metabolism Microscopy, Confocal Peptide Hydrolases / pharmacology* Streptococcus pyogenes / metabolism*, pathogenicity Virulence |
| Grant Support | |
ID/Acronym/Agency:
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HL-30914/HL/NHLBI NIH HHS; HL-56865/HL/NHLBI NIH HHS; R01 HL030914-22/HL/NHLBI NIH HHS; R01 HL056865-10/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Boron Compounds; 0/Cholesterol Esters; 0/Cholesterol, HDL; 0/opacity factor; 151736-99-1/cholesteryl 4,4-difluoro-5,7-dimethyl-4-bora-3,4-diaza-3-indacenedodecanoate; EC 3.4.-/Peptide Hydrolases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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