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

This Article Full Text Full Text (PDF) Alert me when this article is cited 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Anderson, K. M. Articles by Marshall, L. A. Search for Related Content PubMed PubMed Citation Articles by Anderson, K. M. Articles by Marshall, L. A. Social Bookmarking                      What's this?

Volume 272, Number 48, Issue of November 28, 1997 pp. 30504-30511
©1997 by The American Society for Biochemistry and Molecular Biology, Inc.

Cytosolic 85-kDa Phospholipase A₂-mediated Release of Arachidonic Acid Is Critical for Proliferation of Vascular Smooth Muscle Cells

(Received for publication, June 26, 1997, and in revised form, August 14, 1997)

From the Departments of Cardiovascular Pharmacology and Immunopharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania 19406

Recent evidence suggests that arachidonic acid (AA) may be involved in regulating cellular proliferation. The predominant mechanism of AA release from cellular phospholipids is via phospholipase A₂ (PLA₂) hydrolysis. The purpose of this study was to examine the roles of the distinct 14-kDa and 85-kDa PLA₂ enzymes in human coronary artery vascular smooth muscle cell (hCAVSMC) proliferation. Cultured hCAVSMCs proliferate in the presence of growth medium with a typical doubling time of 30-40 h, grow at a slower proliferative rate upon reaching confluency (day 8), and eventually undergo contact inhibition of growth (day 10). Neither Type II 14-kDa PLA₂ activity nor mass changed over a 10-day culture period. In contrast, 85-kDa PLA₂ protein activity and mRNA decreased as time in culture progressed. This reduction in 85-kDa PLA₂ correlated with reductions in DNA synthesis and suggested a possible association between 85-kDa PLA₂ and proliferation. To directly evaluate the role of the 85-kDa PLA₂ in proliferation we examined the effects of an 85-kDa PLA₂ inhibitor (AACOCF₃) and 85-kDa PLA₂ antisense oligonucleotides on proliferation. Both reagents dose dependently inhibited proliferation, whereas a 14-kDa PLA₂ inhibitor (SB203347), a calcium-independent PLA₂ inhibitor (HELSS), an 85-kDa sense oligonucleotide, and a nonrelevant scrambled control oligonucleotide had no effect. The mechanism by which 85-kDa PLA₂ influences cellular proliferation remains unclear. Inhibition of 85-kDa PLA₂ activity produced neither phase-specific cell cycle arrest nor apoptosis (fluorescence-activated cell sorter analysis). Addition of AA (20 µM) attenuated the effects of both AACOCF₃ and 85-kDa antisense oligonucleotides implicating AA as a key mediator in cellular proliferation. However, although prostaglandin E₂ (PGE₂) was present in the culture medium, it peaked early (day 3) in culture, and indomethacin had no effect on cellular proliferation indicating that hCAVSMC proliferation was not mediated through PGE₂. These data provide the first direct evidence that PLA₂ is involved in control of VSMC proliferation and indicate that 85-kDa PLA₂-mediated liberation of AA is critical for cellular proliferation.

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

This article has been cited by other articles:

				N. Gluck, O. Schwob, M. Krimsky, and S. Yedgar Activation of cytosolic phospholipase A2 and fatty acid transacylase is essential but not sufficient for thrombin-induced smooth muscle cell proliferation Am J Physiol Cell Physiol, June 1, 2008; 294(6): C1597 - C1603. [Abstract] [Full Text] [PDF]

				F. Li, C. Zhang, S. Schaefer, A. Estes, and K. U. Malik ANG II-induced neointimal growth is mediated via cPLA2- and PLD2-activated Akt in balloon-injured rat carotid artery Am J Physiol Heart Circ Physiol, December 1, 2005; 289(6): H2592 - H2601. [Abstract] [Full Text] [PDF]

				F. Li and K. U. Malik Angiotensin II-induced Akt activation is mediated by metabolites of arachidonic acid generated by CaMKII-stimulated Ca2+-dependent phospholipase A2 Am J Physiol Heart Circ Physiol, May 1, 2005; 288(5): H2306 - H2316. [Abstract] [Full Text] [PDF]

				A. A Soler-Garcia, R. Maitra, V. Kumar, T. Ise, S. Nagata, R. Beers, T. K Bera, and I. Pastan The PATE gene is expressed in the accessory tissues of the human male genital tract and encodes a secreted sperm-associated protein Reproduction, April 1, 2005; 129(4): 515 - 524. [Abstract] [Full Text] [PDF]

				C. R. Yellaturu and G. N. Rao A Requirement for Calcium-independent Phospholipase A2 in Thrombin-induced Arachidonic Acid Release and Growth in Vascular Smooth Muscle Cells J. Biol. Chem., October 31, 2003; 278(44): 43831 - 43837. [Abstract] [Full Text] [PDF]

				Y. Kawanabe, K. Nozaki, N. Hashimoto, and T. Masaki Characterization of Ca2+ Channels and G Proteins Involved in Arachidonic Acid Release by Endothelin-1/EndothelinA Receptor Mol. Pharmacol., September 1, 2003; 64(3): 689 - 695. [Abstract] [Full Text] [PDF]

				L. Ragolia, T. Palaia, E. Paric, and J. K. Maesaka Prostaglandin D2 Synthase Inhibits the Exaggerated Growth Phenotype of Spontaneously Hypertensive Rat Vascular Smooth Muscle Cells J. Biol. Chem., June 6, 2003; 278(24): 22175 - 22181. [Abstract] [Full Text] [PDF]

				C. R. Yellaturu and G. N. Rao Cytosolic Phospholipase A2 Is an Effector of Jak/STAT Signaling and Is Involved in Platelet-derived Growth Factor BB-induced Growth in Vascular Smooth Muscle Cells J. Biol. Chem., March 7, 2003; 278(11): 9986 - 9992. [Abstract] [Full Text] [PDF]

				S. Bousserouel, A. Brouillet, G. Bereziat, M. Raymondjean, and M. Andreani Different effects of n-6 and n-3 polyunsaturated fatty acids on the activation of rat smooth muscle cells by interleukin-1{beta} J. Lipid Res., March 1, 2003; 44(3): 601 - 611. [Abstract] [Full Text] [PDF]

				S. Fatima, F. A. Yaghini, A. Ahmed, Z. Khandekar, and K. U. Malik CaM kinase II{alpha} mediates norepinephrine-induced translocation of cytosolic phospholipase A2 to the nuclear envelope J. Cell Sci., January 15, 2003; 116(2): 353 - 365. [Abstract] [Full Text] [PDF]

				T.-Y. Chin, H.-M. Hwang, and S.-H. Chueh Distinct Effects of Different Calcium-Mobilizing Agents on Cell Death in NG108-15 Neuroblastoma X Glioma Cells Mol. Pharmacol., March 1, 2002; 61(3): 486 - 494. [Abstract] [Full Text] [PDF]

				J. Jiang, B. L. Neubauer, J. R. Graff, M. Chedid, J. E. Thomas, N. W. Roehm, S. Zhang, G. J. Eckert, M. O. Koch, J. N. Eble, et al. Expression of Group IIA Secretory Phospholipase A2 Is Elevated in Prostatic Intraepithelial Neoplasia and Adenocarcinoma Am. J. Pathol., February 1, 2002; 160(2): 667 - 671. [Abstract] [Full Text] [PDF]

				M. M. Muthalif, Y. Hefner, S. Canaan, J. Harper, H. Zhou, J.-H. Parmentier, R. Aebersold, M. H. Gelb, and K. U. Malik Functional Interaction of Calcium-/Calmodulin-dependent Protein Kinase II and Cytosolic Phospholipase A2 J. Biol. Chem., October 19, 2001; 276(43): 39653 - 39660. [Abstract] [Full Text] [PDF]

				M. M. Muthalif, F. Ljuca, J. B. Roaten, N. Pentapaty, M. R. Uddin, and K. U. Malik Ca2+/Calmodulin-Dependent Protein Kinase II and Cytosolic Phospholipase A2 Contribute to Mitogenic Signaling in Myeloblastic Leukemia U-937 Cells J. Pharmacol. Exp. Ther., July 1, 2001; 298(1): 272 - 278. [Abstract] [Full Text]

				C. Couturier, V. Antonio, A. Brouillet, G. Bereziat, M. Raymondjean, and M. Andreani Protein Kinase A-Dependent Stimulation of Rat Type II Secreted Phospholipase A2 Gene Transcription Involves C/EBP-{beta} and -{{delta}} in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., December 1, 2000; 20(12): 2559 - 2565. [Abstract] [Full Text] [PDF]

				J. Marshall, E. Krump, T. Lindsay, G. Downey, D. A. Ford, P. Zhu, P. Walker, and B. Rubin Involvement of Cytosolic Phospholipase A2 and Secretory Phospholipase A2 in Arachidonic Acid Release from Human Neutrophils J. Immunol., February 15, 2000; 164(4): 2084 - 2091. [Abstract] [Full Text] [PDF]

				A. J. Trimboli, B. M. Waite, G.-i. Atsumi, A. N. Fonteh, A. M. Namen, C. E. Clay, T. E. Kute, K. P. High, M. C. Willingham, and F. H. Chilton Influence of Coenzyme A-independent Transacylase and Cyclooxygenase Inhibitors on the Proliferation of Breast Cancer Cells Cancer Res., December 1, 1999; 59(24): 6171 - 6177. [Abstract] [Full Text] [PDF]

				M. G. Frid, A. A. Aldashev, R. A. Nemenoff, R. Higashito, J. Y. Westcott, and K. R. Stenmark Subendothelial Cells From Normal Bovine Arteries Exhibit Autonomous Growth and Constitutively Activated Intracellular Signaling Arterioscler. Thromb. Vasc. Biol., December 1, 1999; 19(12): 2884 - 2893. [Abstract] [Full Text] [PDF]

				M. T. Rizzo, E. Regazzi, D. Garau, L. Akard, M. Dugan, H. S. Boswell, V. Rizzoli, and C. Carlo-Stella Induction of Apoptosis by Arachidonic Acid in Chronic Myeloid Leukemia Cells Cancer Res., October 1, 1999; 59(19): 5047 - 5053. [Abstract] [Full Text] [PDF]

				H. M. Schuller, P. K. Tithof, M. Williams, and H. Plummer III The Tobacco-specific Carcinogen 4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanone Is a {beta}-Adrenergic Agonist and Stimulates DNA Synthesis in Lung Adenocarcinoma via {beta}-Adrenergic Receptor-mediated Release of Arachidonic Acid Cancer Res., September 1, 1999; 59(18): 4510 - 4515. [Abstract] [Full Text] [PDF]

				C. Couturier, A. Brouillet, C. Couriaud, K. Koumanov, G. Bereziat, and M. Andreani Interleukin 1beta Induces Type II-secreted Phospholipase A2 Gene in Vascular Smooth Muscle Cells by a Nuclear Factor kappa B and Peroxisome Proliferator-activated Receptor-mediated Process J. Biol. Chem., August 13, 1999; 274(33): 23085 - 23093. [Abstract] [Full Text] [PDF]

				N. O. Dulin, A. Sorokin, and J. G. Douglas Arachidonate-Induced Tyrosine Phosphorylation of Epidermal Growth Factor Receptor and Shc-Grb2-Sos Association Hypertension, December 1, 1998; 32(6): 1089 - 1093. [Abstract] [Full Text] [PDF]

				M. M. Muthalif, I. F. Benter, N. Karzoun, S. Fatima, J. Harper, M. R. Uddin, and K. U. Malik 20-Hydroxyeicosatetraenoic acid mediates calcium/calmodulin-dependent protein kinase II-induced mitogen-activated protein kinase activation in vascular smooth muscle cells PNAS, October 13, 1998; 95(21): 12701 - 12706. [Abstract] [Full Text] [PDF]

				A. K. Roshak, E. A. Capper, C. Stevenson, C. Eichman, and L. A. Marshall Human Calcium-independent Phospholipase A2 Mediates Lymphocyte Proliferation J. Biol. Chem., November 10, 2000; 275(46): 35692 - 35698. [Abstract] [Full Text] [PDF]

				H. Peilot, B. Rosengren, G. Bondjers, and E. Hurt-Camejo Interferon-gamma Induces Secretory Group IIA Phospholipase A2 in Human Arterial Smooth Muscle Cells. INVOLVEMENT OF CELL DIFFERENTIATION, STAT-3 ACTIVATION, AND MODULATION BY OTHER CYTOKINES J. Biol. Chem., July 21, 2000; 275(30): 22895 - 22904. [Abstract] [Full Text] [PDF]

				A. N. Fonteh, T. LaPorte, D. Swan, and M. A. McAlexander A Decrease in Remodeling Accounts for the Accumulation of Arachidonic Acid in Murine Mast Cells Undergoing Apoptosis J. Biol. Chem., January 5, 2001; 276(2): 1439 - 1449. [Abstract] [Full Text] [PDF]

				C. S. T. Hii, N. Moghadammi, A. Dunbar, and A. Ferrante Activation of the Phosphatidylinositol 3-Kinase-Akt/Protein Kinase B Signaling Pathway in Arachidonic Acid-stimulated Human Myeloid and Endothelial Cells. INVOLVEMENT OF THE ErbB RECEPTOR FAMILY J. Biol. Chem., July 13, 2001; 276(29): 27246 - 27255. [Abstract] [Full Text] [PDF]

				M. W. Anthonsen, S. Andersen, A. Solhaug, and B. Johansen Atypical lambda /iota PKC Conveys 5-Lipoxygenase/Leukotriene B4-mediated Cross-talk between Phospholipase A2s Regulating NF-kappa B Activation in Response to Tumor Necrosis Factor-alpha and Interleukin-1beta J. Biol. Chem., September 14, 2001; 276(38): 35344 - 35351. [Abstract] [Full Text] [PDF]