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

J. Biol. Chem., Vol. 281, Issue 31, 22275-22288, August 4, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/31/22275    most recent M604330200v1 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 Seleznev, K. Articles by Ma, Z. A. Search for Related Content PubMed PubMed Citation Articles by Seleznev, K. Articles by Ma, Z. A. Social Bookmarking                      What's this?

Calcium-independent Phospholipase A₂ Localizes in and Protects Mitochondria during Apoptotic Induction by Staurosporine^*

From the Division of Experimental Diabetes and Aging, Department of Geriatrics and Adult Development, Mount Sinai School of Medicine, New York, New York 10029

Mitochondria-mediated production of reactive oxygen species (ROS) plays a key role in apoptosis. Mitochondrial phospholipid cardiolipin molecules are likely the main target of ROS because they are particularly rich in polyunsaturated fatty acids. They are also located in the inner mitochondrial membrane near the ROS-producing sites. Under physiological conditions mitochondria can repair peroxidative damage in part through a remodeling mechanism via the deacylation-reacylation cycle mediated by phospholipase A₂ (PLA₂) and acyl-coenzyme A-dependent monolysocardiolipin acyltransferase. Here we investigate whether group VIA Ca²⁺-independent PLA₂ (iPLA₂) plays a role in the protection of mitochondrial function from damage caused by mitochondrially generated ROS during apoptotic induction by staurosporine (STS). We show that iPLA₂-expressing cells were relatively resistant to STS-induced apoptosis. iPLA₂ localized to mitochondria even before apoptotic induction, and most iPLA₂-associated mitochondria were intact in apoptotic resistant cells. Expression of iPLA₂ in INS-1 cells prevented the loss of mitochondrial membrane potential, attenuated the release of cytochrome c, Smac/DIABLO, and apoptosis inducing factor from mitochondria, and reduced mitochondrial reactive oxygen species production. Inhibition of caspase 8 has little effect on STS-induced apoptosis in INS-1 cells. Finally, we found that STS down-regulated endogenous iPLA₂ transcription in both INS-1 and iPLA₂-expressing INS-1 cells without affecting the expression of group IV Ca²⁺-dependent PLA₂. Together, our data indicate that iPLA₂ is important for the protection of mitochondrial function from oxidative damage during apoptotic induction. Down-regulation of endogenous iPLA₂ by STS may result in the loss of mitochondrial membrane repair functions and lead to mitochondrial failure and apoptosis.

Received for publication, May 5, 2006

^* This work is supported by grants from the NIDDK, National Institutes of Health and the Juvenile Diabetes Research Foundation, International. 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.

¹ To whom correspondence should be addressed. Tel.: 212-241-5651; Fax: 212-241-7248; E-mail: zhongmin.ma{at}mssm.edu.

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

This article has been cited by other articles:

				Z. Zhao, C. Zhao, X. H. Zhang, F. Zheng, W. Cai, H. Vlassara, and Z. A. Ma Advanced Glycation End Products Inhibit Glucose-Stimulated Insulin Secretion through Nitric Oxide-Dependent Inhibition of Cytochrome c Oxidase and Adenosine Triphosphate Synthesis Endocrinology, June 1, 2009; 150(6): 2569 - 2576. [Abstract] [Full Text] [PDF]

				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]

				S. B. Widenmaier, A. V. Sampaio, T. M. Underhill, and C. H. S. McIntosh Noncanonical Activation of Akt/Protein Kinase B in {beta}-Cells by the Incretin Hormone Glucose-dependent Insulinotropic Polypeptide J. Biol. Chem., April 17, 2009; 284(16): 10764 - 10773. [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. Malhotra, I. Edelman-Novemsky, Y. Xu, H. Plesken, J. Ma, M. Schlame, and M. Ren Role of calcium-independent phospholipase A2 in the pathogenesis of Barth syndrome PNAS, February 17, 2009; 106(7): 2337 - 2341. [Abstract] [Full Text] [PDF]

				G. R. Kinsey, J. L. Blum, M. D. Covington, B. S. Cummings, J. McHowat, and R. G. Schnellmann Decreased iPLA2{gamma} expression induces lipid peroxidation and cell death and sensitizes cells to oxidant-induced apoptosis J. Lipid Res., July 1, 2008; 49(7): 1477 - 1487. [Abstract] [Full Text] [PDF]

				K. Shinzawa, H. Sumi, M. Ikawa, Y. Matsuoka, M. Okabe, S. Sakoda, and Y. Tsujimoto Neuroaxonal Dystrophy Caused by Group VIA Phospholipase A2 Deficiency in Mice: A Model of Human Neurodegenerative Disease J. Neurosci., February 27, 2008; 28(9): 2212 - 2220. [Abstract] [Full Text] [PDF]

				V. Kainu, M. Hermansson, and P. Somerharju Electrospray Ionization Mass Spectrometry and Exogenous Heavy Isotope-labeled Lipid Species Provide Detailed Information on Aminophospholipid Acyl Chain Remodeling J. Biol. Chem., February 8, 2008; 283(6): 3676 - 3687. [Abstract] [Full Text] [PDF]

				X. H. Zhang, C. Zhao, and Z. A. Ma The increase of cell-membranous phosphatidylcholines containing polyunsaturated fatty acid residues induces phosphorylation of p53 through activation of ATR J. Cell Sci., December 1, 2007; 120(23): 4134 - 4143. [Abstract] [Full Text] [PDF]

				V. Appay, A. Bosio, S. Lokan, Y. Wiencek, C. Biervert, D. Kusters, E. Devevre, D. Speiser, P. Romero, N. Rufer, et al. Sensitive Gene Expression Profiling of Human T Cell Subsets Reveals Parallel Post-Thymic Differentiation for CD4+ and CD8+ Lineages J. Immunol., December 1, 2007; 179(11): 7406 - 7414. [Abstract] [Full Text] [PDF]

				D. J. Mancuso, H. F. Sims, X. Han, C. M. Jenkins, S. P. Guan, K. Yang, S. H. Moon, T. Pietka, N. A. Abumrad, P. H. Schlesinger, et al. Genetic Ablation of Calcium-independent Phospholipase A2{gamma} Leads to Alterations in Mitochondrial Lipid Metabolism and Function Resulting in a Deficient Mitochondrial Bioenergetic Phenotype J. Biol. Chem., November 30, 2007; 282(48): 34611 - 34622. [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]

				B. Benassi, G. Zupi, and A. Biroccio {gamma}-Glutamylcysteine Synthetase Mediates the c-Myc-Dependent Response to Antineoplastic Agents in Melanoma Cells Mol. Pharmacol., October 1, 2007; 72(4): 1015 - 1023. [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]

				R. Chen, L. Yang, and T. M. McIntyre Cytotoxic Phospholipid Oxidation Products: CELL DEATH FROM MITOCHONDRIAL DAMAGE AND THE INTRINSIC CASPASE CASCADE J. Biol. Chem., August 24, 2007; 282(34): 24842 - 24850. [Abstract] [Full Text] [PDF]

				G. R. Kinsey, J. McHowat, K. S. Patrick, and R. G. Schnellmann Role of Ca2+-Independent Phospholipase A2{gamma} in Ca2+-Induced Mitochondrial Permeability Transition J. Pharmacol. Exp. Ther., May 1, 2007; 321(2): 707 - 715. [Abstract] [Full Text] [PDF]

				G. R. Kinsey, J. McHowat, C. S. Beckett, and R. G. Schnellmann Identification of calcium-independent phospholipase A2{gamma} in mitochondria and its role in mitochondrial oxidative stress Am J Physiol Renal Physiol, February 1, 2007; 292(2): F853 - F860. [Abstract] [Full Text] [PDF]