Document Detail


Arachidonate release and prostaglandin production by group IVC phospholipase A2 (cytosolic phospholipase A2gamma).
MedLine Citation:
PMID:  12611587     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
While the role of the group IVA Ca(2+)-dependent cytosolic phospholipase A(2)alpha (cPLA(2)alpha) in arachidonic acid (AA) metabolism has been well documented, that of its paralogue, Ca(2+)-independent group IVC PLA(2) (cPLA(2)gamma), has remained uncertain. Here we show, using a transfection strategy, that cPLA(2)gamma has the ability to increase the spontaneous and stimulus-induced release of cellular fatty acids. The AA released by cPLA(2)gamma was metabolized further to prostaglandin E(2) via cyclo-oxygenase-1 (COX-1) in the immediate response, and via COX-2 in the delayed response. Mutation of the putative catalytic-centre residue Ser(82) abrogated the AA-releasing function of cPLA(2)gamma both in vitro and in vivo. Confocal microscopy revealed that cPLA(2)gamma was distributed in the perinuclear endoplasmic reticulum membranes. Mutating the C-terminal prenylation site of cPLA(2)gamma abrogated its intracellular membrane localization and cellular AA-releasing function, without reducing its enzyme activity in vitro. Our results indicate that cPLA(2)gamma is the second cPLA(2) enzyme that contributes to cellular AA metabolism and phospholipid remodelling under appropriate conditions.
Authors:
Makoto Murakami; Seiko Masuda; Ichiro Kudo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Biochemical journal     Volume:  372     ISSN:  0264-6021     ISO Abbreviation:  Biochem. J.     Publication Date:  2003 Jun 
Date Detail:
Created Date:  2003-06-04     Completed Date:  2003-07-23     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  2984726R     Medline TA:  Biochem J     Country:  England    
Other Details:
Languages:  eng     Pagination:  695-702     Citation Subset:  IM    
Affiliation:
Department of Health Chemistry, School of Pharmaceutical Sciences, Showa University, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8555, Japan. mako@pharm.showa-u.ac.jp
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Substitution
Animals
Arachidonic Acid / metabolism*
Arachidonic Acids / pharmacology
Binding Sites
Blotting, Northern
Cells, Cultured
Cyclooxygenase 1
Cyclooxygenase 2
Cytosol / enzymology
DNA, Complementary / genetics
Endoplasmic Reticulum / metabolism
Humans
Isoenzymes / antagonists & inhibitors,  chemistry,  metabolism
Membrane Proteins
Mice
Microscopy, Confocal
Nitrobenzenes / pharmacology
Phospholipases A / antagonists & inhibitors,  chemistry,  genetics,  metabolism*
Phospholipases A2
Phosphonic Acids / pharmacology
Prostaglandin-Endoperoxide Synthases / chemistry,  metabolism
Prostaglandins / biosynthesis*
Sulfonamides / pharmacology
Transfection / methods
Chemical
Reg. No./Substance:
0/Arachidonic Acids; 0/DNA, Complementary; 0/Isoenzymes; 0/Membrane Proteins; 0/Nitrobenzenes; 0/Phosphonic Acids; 0/Prostaglandins; 0/Sulfonamides; 0/methyl arachidonylfluorophosphonate; 123653-11-2/N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; 506-32-1/Arachidonic Acid; EC 1.14.99.1/Cyclooxygenase 1; EC 1.14.99.1/Cyclooxygenase 2; EC 1.14.99.1/PTGS1 protein, human; EC 1.14.99.1/PTGS2 protein, human; EC 1.14.99.1/Prostaglandin-Endoperoxide Synthases; EC 1.14.99.1/Ptgs1 protein, mouse; EC 3.1.1.-/Phospholipases A; EC 3.1.1.4/Phospholipases A2
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