| Antisense inhibition of group VI Ca2+-independent phospholipase A2 blocks phospholipid fatty acid remodeling in murine P388D1 macrophages. | |
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MedLine Citation:
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PMID: 9361012 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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J Balsinde; M A Balboa; E A Dennis |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 272 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 1997 Nov |
Date Detail:
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Created Date: 1997-12-11 Completed Date: 1997-12-11 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 29317-21 Citation Subset: IM |
Affiliation:
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Department of Chemistry and Biochemistry, University of California at San Diego, La Jolla, California 92093-0601, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Arachidonic Acid / metabolism* Calcium / metabolism* Leukemia P388 / metabolism* Membrane Lipids / metabolism Mice Naphthalenes / pharmacology Oligonucleotides, Antisense / pharmacology* Phospholipases A / antagonists & inhibitors*, metabolism Phospholipases A2 Phospholipids / metabolism* Pyrones / pharmacology |
| Grant Support | |
ID/Acronym/Agency:
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GM 20501/GM/NIGMS NIH HHS; HD 26171/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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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 3.1.1.4/Phospholipases A2 |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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