Document Detail

Antisense inhibition of group VI Ca2+-independent phospholipase A2 blocks phospholipid fatty acid remodeling in murine P388D1 macrophages.
MedLine Citation:
PMID:  9361012     Owner:  NLM     Status:  MEDLINE    
A major issue in lipid signaling relates to the role of particular phospholipase A2 isoforms in mediating receptor-triggered responses. This has been difficult to study because of the lack of isoform-specific inhibitors. Based on the use of the Group VI Ca2+-independent phospholipase A2 (iPLA2) inhibitor bromoenol lactone (BEL), we previously suggested a role for the iPLA2 in mediating phospholipid fatty acid turnover (Balsinde, J., Bianco, I. D., Ackermann, E. J., Conde-Frieboes, K., and Dennis, E. A. (1995) Proc. Natl. Acad. Sci. U. S. A. 92: 8527-8531). We have now further evaluated the role of the iPLA2 in phospholipid remodeling by using antisense RNA technology. We show herein that inhibition of iPLA2 expression by a specific antisense oligonucleotide decreases both the steady-state levels of lysophosphatidylcholine and the capacity of the cell to incorporate arachidonic acid into membrane phospholipids. These effects correlate with a decrease in both iPLA2 activity and protein in the antisense-treated cells. Collectively these data provide further evidence that the iPLA2 plays a major role in regulating phospholipid fatty acyl turnover in P388D1 macrophages. In stark contrast, experiments with activated cells confirmed that the iPLA2 does not play a significant role in receptor-coupled arachidonate mobilization in these cells, as manifested by the lack of an effect of the iPLA2 antisense oligonucleotide on PAF-stimulated arachidonate release.
J Balsinde; M A Balboa; E A Dennis
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  272     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  1997 Nov 
Date Detail:
Created Date:  1997-12-11     Completed Date:  1997-12-11     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  29317-21     Citation Subset:  IM    
Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0601, USA.
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MeSH Terms
Arachidonic Acid / metabolism*
Calcium / metabolism*
Leukemia P388 / metabolism*
Membrane Lipids / metabolism
Naphthalenes / pharmacology
Oligonucleotides, Antisense / pharmacology*
Phospholipases A / antagonists & inhibitors*,  metabolism
Phospholipases A2
Phospholipids / metabolism*
Pyrones / pharmacology
Grant Support
Reg. No./Substance:
0/Membrane Lipids; 0/Naphthalenes; 0/Oligonucleotides, Antisense; 0/Phospholipids; 0/Pyrones; 506-32-1/Arachidonic Acid; 7440-70-2/Calcium; 88070-98-8/6-(bromomethylene)tetrahydro-3-(1-naphthaleneyl)-2H-pyran-2-one; EC 3.1.1.-/Phospholipases A; EC A2

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