HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 279, Issue 39, 40385-40391, September 24, 2004

This Article Full Text Full Text (PDF) All Versions of this Article: 279/39/40385    most recent M402562200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Pérez, R. Articles by Balsinde, J. Search for Related Content PubMed PubMed Citation Articles by Pérez, R. Articles by Balsinde, J. Social Bookmarking                      What's this?

Role of Group VIA Calcium-independent Phospholipase A₂ in Arachidonic Acid Release, Phospholipid Fatty Acid Incorporation, and Apoptosis in U937 Cells Responding to Hydrogen Peroxide^*

Rebeca Pérez, Roberto Melero, María A. Balboa, and Jesús Balsinde

From the Institute of Molecular Biology and Genetics, University of Valladolid School of Medicine, 47005 Valladolid, Spain

Group VIA calcium-independent phospholipase A₂ (iPLA₂) has been shown to play a major role in regulating basal phospholipid deacylation reactions in certain cell types. More recently, roles for this enzyme have also been suggested in the destruction of membrane phospholipid during apoptosis and after oxidant injury. Proposed iPLA₂ roles have rested heavily on the use of bromoenol lactone as an iPLA₂-specific inhibitor, but this compound actually inhibits other enzymes and lipid pathways unrelated to PLA₂, which makes it difficult to define the contribution of iPLA₂ to specific functions. In previous work, we pioneered the use of antisense technology to decrease cellular iPLA₂ activity as an alternative approach to study iPLA₂ functions. In the present study, we followed the opposite strategy and prepared U937 cells that exhibited enhanced iPLA activity by stably expressing a plasmid containing iPLA₂ cDNA. Compared with control cells, the iPLA₂ -overexpressing U937 cells showed elevated responses to hydrogen peroxide with regard to both arachidonic acid mobilization and incorporation of the fatty acid into phospholipids, thus providing additional evidence for the key role that iPLA₂ plays in these events. Long-term exposure of the cells to hydrogen peroxide resulted in cell death by apoptosis, and this process was accelerated in the iPLA₂-overexpressing cells. Increased phospholipid hydrolysis and fatty acid release also occurred in these cells. Unexpectedly, however, abrogation of U937 cell iPLA₂ activity by either methyl arachidonyl fluorophosphonate or an antisense oligonucleotide did not delay or decrease the extent of apoptosis induced by hydrogen peroxide. These results indicate that, although iPLA₂-mediated phospholipid hydrolysis occurs during apoptosis, iPLA₂ may actually be dispensable for the apoptotic process to occur. Thus, beyond a mere destructive role, iPLA₂ may play other roles during apoptosis.

Received for publication, March 8, 2004 , and in revised form, June 9, 2004.

^* This work was supported by Grant BMC2001-2244 from the Spanish Ministry of Science and Technology, Grant CSI-4/02 from the Education Department of the Autonomous Government of Castile and León, and Grant 011232 from the Fundació La Marató de TV3. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: IBGM-CSIC, Facultad de Medicina, Universidad de Valladolid, Avenida Ramón y Cajal 7, 47005 Valladolid, Spain. Tel.: 34-983-423-062; Fax: 34-983-423-588; E-mail: jbalsinde{at}ibgm.uva.es.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				A.-D. Andersen, K. A. Poulsen, I. H. Lambert, and S. F. Pedersen HL-1 mouse cardiomyocyte injury and death after simulated ischemia and reperfusion: roles of pH, Ca2+-independent phospholipase A2, and Na+/H+ exchange Am J Physiol Cell Physiol, May 1, 2009; 296(5): C1227 - C1242. [Abstract] [Full Text] [PDF]

				V. Ruiperez, A. M. Astudillo, M. A. Balboa, and J. Balsinde Coordinate Regulation of TLR-Mediated Arachidonic Acid Mobilization in Macrophages by Group IVA and Group V Phospholipase A2s J. Immunol., March 15, 2009; 182(6): 3877 - 3883. [Abstract] [Full Text] [PDF]

				A. Gubern, M. Barcelo-Torns, J. Casas, D. Barneda, R. Masgrau, F. Picatoste, J. Balsinde, M. A. Balboa, and E. Claro Lipid Droplet Biogenesis Induced by Stress Involves Triacylglycerol Synthesis That Depends on Group VIA Phospholipase A2 J. Biol. Chem., February 27, 2009; 284(9): 5697 - 5708. [Abstract] [Full Text] [PDF]

				A Gregory, B J Polster, and S J Hayflick Clinical and genetic delineation of neurodegeneration with brain iron accumulation J. Med. Genet., February 1, 2009; 46(2): 73 - 80. [Abstract] [Full Text] [PDF]

				A. B. Herrero, A. M. Astudillo, M. A. Balboa, C. Cuevas, J. Balsinde, and S. Moreno Levels of SCS7/FA2H-Mediated Fatty Acid 2-Hydroxylation Determine the Sensitivity of Cells to Antitumor PM02734 Cancer Res., December 1, 2008; 68(23): 9779 - 9787. [Abstract] [Full Text] [PDF]

				K. A. Poulsen, S. F. Pedersen, M. Kolko, and I. H. Lambert Induction of group VIA phospholipase A2 activity during in vitro ischemia in C2C12 myotubes is associated with changes in the level of its splice variants Am J Physiol Cell Physiol, November 1, 2007; 293(5): C1605 - C1615. [Abstract] [Full Text] [PDF]

				L. Blanc, C. Barres, P. Bette-Bobillo, and M. Vidal Reticulocyte-secreted exosomes bind natural IgM antibodies: involvement of a ROS-activatable endosomal phospholipase iPLA2 Blood, November 1, 2007; 110(9): 3407 - 3416. [Abstract] [Full Text] [PDF]

				J. Pindado, J. Balsinde, and M. A. Balboa TLR3-Dependent Induction of Nitric Oxide Synthase in RAW 264.7 Macrophage-Like Cells via a Cytosolic Phospholipase A2/Cyclooxygenase-2 Pathway J. Immunol., October 1, 2007; 179(7): 4821 - 4828. [Abstract] [Full Text] [PDF]

				S. Bao, Y. Li, X. Lei, M. Wohltmann, W. Jin, A. Bohrer, C. F. Semenkovich, S. Ramanadham, I. Tabas, and J. Turk Attenuated Free Cholesterol Loading-induced Apoptosis but Preserved Phospholipid Composition of Peritoneal Macrophages from Mice That Do Not Express Group VIA Phospholipase A2 J. Biol. Chem., September 14, 2007; 282(37): 27100 - 27114. [Abstract] [Full Text] [PDF]

				V. Ruiperez, J. Casas, M. A. Balboa, and J. Balsinde Group V Phospholipase A2-Derived Lysophosphatidylcholine Mediates Cyclooxygenase-2 Induction in Lipopolysaccharide-Stimulated Macrophages J. Immunol., July 1, 2007; 179(1): 631 - 638. [Abstract] [Full Text] [PDF]

				P. A. Wilson, S. D. Gardner, N. M. Lambie, S. A. Commans, and D. J. Crowther Characterization of the human patatin-like phospholipase family J. Lipid Res., September 1, 2006; 47(9): 1940 - 1949. [Abstract] [Full Text] [PDF]

				A. A. Farooqui, W.-Y. Ong, and L. A. Horrocks Inhibitors of Brain Phospholipase A2 Activity: Their Neuropharmacological Effects and Therapeutic Importance for the Treatment of Neurologic Disorders Pharmacol. Rev., September 1, 2006; 58(3): 591 - 620. [Abstract] [Full Text] [PDF]

				G. Saavedra, W. Zhang, B. Peterson, and B. S. Cummings Differential Roles for Cytosolic and Microsomal Ca2+-Independent Phospholipase A2 in Cell Growth and Maintenance of Phospholipids J. Pharmacol. Exp. Ther., September 1, 2006; 318(3): 1211 - 1219. [Abstract] [Full Text] [PDF]

				K. Seleznev, C. Zhao, X. H. Zhang, K. Song, and Z. A. Ma Calcium-independent Phospholipase A2 Localizes in and Protects Mitochondria during Apoptotic Induction by Staurosporine J. Biol. Chem., August 4, 2006; 281(31): 22275 - 22288. [Abstract] [Full Text] [PDF]

				S. Bao, H. Song, M. Wohltmann, S. Ramanadham, W. Jin, A. Bohrer, and J. Turk Insulin Secretory Responses and Phospholipid Composition of Pancreatic Islets from Mice That Do Not Express Group VIA Phospholipase A2 and Effects of Metabolic Stress on Glucose Homeostasis J. Biol. Chem., July 28, 2006; 281(30): 20958 - 20973. [Abstract] [Full Text] [PDF]

				J. Y. Kim, K. Tillison, J.-H. Lee, D. A. Rearick, and C. M. Smas The adipose tissue triglyceride lipase ATGL/PNPLA2 is downregulated by insulin and TNF-{alpha} in 3T3-L1 adipocytes and is a target for transactivation by PPAR{gamma} Am J Physiol Endocrinol Metab, July 1, 2006; 291(1): E115 - E127. [Abstract] [Full Text] [PDF]

				J. Casas, M. A. Gijon, A. G. Vigo, M. S. Crespo, J. Balsinde, and M. A. Balboa Overexpression of Cytosolic Group IVA Phospholipase A2 Protects Cells from Ca2+-dependent Death J. Biol. Chem., March 3, 2006; 281(9): 6106 - 6116. [Abstract] [Full Text] [PDF]

				R. Perez, X. Matabosch, A. Llebaria, M. A. Balboa, and J. Balsinde Blockade of arachidonic acid incorporation into phospholipids induces apoptosis in U937 promonocytic cells J. Lipid Res., March 1, 2006; 47(3): 484 - 491. [Abstract] [Full Text] [PDF]

				R. Perez, M. A. Balboa, and J. Balsinde Involvement of Group VIA Calcium-Independent Phospholipase A2 in Macrophage Engulfment of Hydrogen Peroxide-Treated U937 Cells J. Immunol., February 15, 2006; 176(4): 2555 - 2561. [Abstract] [Full Text] [PDF]

				S. Bao, A. Bohrer, S. Ramanadham, W. Jin, S. Zhang, and J. Turk Effects of Stable Suppression of Group VIA Phospholipase A2 Expression on Phospholipid Content and Composition, Insulin Secretion, and Proliferation of INS-1 Insulinoma Cells J. Biol. Chem., January 6, 2006; 281(1): 187 - 198. [Abstract] [Full Text] [PDF]

				J. Casas, M. A. Gijon, A. G. Vigo, M. S. Crespo, J. Balsinde, and M. A. Balboa Phosphatidylinositol 4,5-Bisphosphate Anchors Cytosolic Group IVA Phospholipase A2 to Perinuclear Membranes and Decreases Its Calcium Requirement for Translocation in Live Cells Mol. Biol. Cell, January 1, 2006; 17(1): 155 - 162. [Abstract] [Full Text] [PDF]