Document Detail

Translocation of phospholipase A2 to membranes by oxidized LDL and hydroxyoctadecadienoic acid to contribute to cholesteryl ester formation.
MedLine Citation:
PMID:  15522824     Owner:  NLM     Status:  MEDLINE    
We examined the mechanisms underlying the activation of group IVA cytosolic phospholipase A(2) (cPLA(2)alpha) contributing to the supply of fatty acids required for the formation of cholesteryl ester in oxidized low-density lipoprotein (oxLDL)-stimulated macrophages. The possible involvement of oxidized lipids was also examined. In [(3)H]arachidonic acid-labeled mouse peritoneal macrophages, oxLDL stimulated the release of arachidonic acid, which was suppressed by methyl arachidonyl fluorophosphonate (MAFP), a cPLA(2)alpha inhibitor. oxLDL induced an increase in PLA(2)alpha levels in the membrane fraction without affecting those in whole cells or the activity in the lysate. Among 13-hydroxyoctadecadienoic acid (13-HODE), 7-ketocholesterol, and 25-hydroxycholesterol, oxidized lipids present in oxLDL particles, only 13-HODE induced the release of arachidonic acid, which was also sensitive to MAFP. Under conditions where addition of Ca(2+) to the cell lysate induced an increase in cPLA(2)alpha protein in the membrane fraction, preincubation with 13-HODE facilitated the Ca(2+)-dependent translocation of cPLA(2)alpha. Furthermore, 13-HODE increased cholesteryl ester formation in the presence of [(3)H]cholesterol. These results suggest that 13-HODE mediates the oxLDL-induced activation of cPLA(2)alpha through an increase in cPLA(2)alpha protein in the membranes, thus contributing, in part, to the supply of fatty acids required for the esterification of cholesterol in macrophages.
Satoshi Akiba; Hiromi Ii; Yukimasa Yoneda; Takashi Sato
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1686     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2004 Nov 
Date Detail:
Created Date:  2004-11-03     Completed Date:  2005-02-08     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  77-84     Citation Subset:  IM    
Department of Pathological Biochemistry, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan.
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MeSH Terms
Arachidonic Acid / antagonists & inhibitors,  biosynthesis
Arachidonic Acids / pharmacology
Calcimycin / pharmacology
Calcium / chemistry,  metabolism
Cell Membrane / enzymology
Cells, Cultured
Cholesterol / chemistry,  metabolism
Cholesterol Esters / biosynthesis*
Cytosol / enzymology
Enzyme Activation / drug effects
Enzyme Inhibitors / pharmacology
Ionophores / pharmacology
Linoleic Acids / metabolism,  pharmacology*
Lipoproteins, LDL / chemistry,  metabolism,  pharmacology*
Macrophages, Peritoneal / drug effects,  metabolism
Phospholipases A / antagonists & inhibitors,  metabolism*
Phospholipases A2
Phosphonic Acids / pharmacology
Protein Transport
Reg. No./Substance:
0/Arachidonic Acids; 0/Cholesterol Esters; 0/Enzyme Inhibitors; 0/Ionophores; 0/Linoleic Acids; 0/Lipoproteins, LDL; 0/Phosphonic Acids; 0/methyl arachidonylfluorophosphonate; 506-32-1/Arachidonic Acid; 5204-88-6/13-hydroxy-9,11-octadecadienoic acid; 52665-69-7/Calcimycin; 57-88-5/Cholesterol; 7440-70-2/Calcium; EC 3.1.1.-/Phospholipases A; EC A2

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