Document Detail


Lipoprotein-associated phospholipase A2 decreases oxidized lipoprotein cellular association by human macrophages and hepatocytes.
MedLine Citation:
PMID:  19895904     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We investigated whether the presence of endogenous or exogenous lipoprotein-associated phospholipase A2 (Lp-PLA2) can modify the cellular association of oxidized low density lipoprotein (oxLDL) and oxidized lipoprotein(a) (oxLp(a)) by human monocyte-derived macrophages (MDM) and hepatocytes (HepG2). Purified recombinant Lp-PLA2 was used as a source of exogenous enzyme whereas Pefabloc (serine esterase inhibitor) was used to inhibit the endogenous Lp-PLA2 activity associated with isolated lipoproteins. Cellular association studies were performed with DiI-labeled oxLDL or oxLp(a) and human monocyte-derived macrophages and HepG2 cells. Active Lp-PLA2 decreased the cellular association of oxLDL and oxLp(a) in macrophages and HepG2 cells by approximately 30-40%, whereas the inactive enzyme did not significantly change oxidized lipoprotein cellular association by either cell type. OxLDL pretreated by Pefabloc increased oxLDL cellular association by MDM and HepG2 cells compared to untreated oxLDL. Therefore, unlike some lipases, Lp-PLA2 did not appear to have any catalytic independent function in oxLDL cellular association. To assess whether the reduced cellular association mediated by Lp-PLA2 was due to the hydrolysis of oxidized phosphatidylcholine (oxPC), we measured the concentration of lysophosphatidylcholine (lysoPC) in lipoprotein fractions after Lp-PLA2 treatment. LysoPC was increased by 20% (0.4 microM) and 87% (0.7 microM) by active Lp-PLA2 compared to inactive Lp-PLA2 for oxLDL and Lp(a), respectively. LysoPC at higher concentration dose-dependently increased the cellular association of oxLDL and oxLp(a) in MDM and HepG2 cells. We conclude that Lp-PLA2 mediates a decrease in oxidized lipoprotein cellular association in human macrophages and HepG2 cells by reducing the concentration of oxPC within these lipoproteins.
Authors:
Ming Yang; Eugene M Chu; Muriel J Caslake; Celina Edelstein; Angelo M Scanu; John S Hill
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2009-11-04
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1801     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2010-02-04     Completed Date:  2010-03-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  176-82     Citation Subset:  IM    
Copyright Information:
2009 Elsevier B.V. All rights reserved.
Affiliation:
James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, Providence Heart+ Lung Institute Department of Pathology and Laboratory Medicine, University of British Columbia-St. Paul's Hospital, Healthy Heart Program, 1081 Burrard Street, Vancouver BC V6Z1Y6, Canada.
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Flow Cytometry
Hepatocytes / metabolism*
Humans
Lipoprotein(a) / metabolism*
Lipoproteins, LDL / metabolism*
Macrophages / metabolism*
Monocytes / metabolism
Phospholipases A2 / genetics,  isolation & purification,  metabolism*
Recombinant Proteins / genetics,  isolation & purification,  metabolism
Grant Support
ID/Acronym/Agency:
HL 63029/HL/NHLBI NIH HHS; MOP74480//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Lipoprotein(a); 0/Lipoproteins, LDL; 0/Recombinant Proteins; 0/oxidized low density lipoprotein; EC 3.1.1.4/Phospholipases A2

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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