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AJP - Renal Physiology, Vol 269, Issue 5 739-F749, Copyright © 1995 by American Physiological Society
ARTICLES |
A. V. Cybulsky, J. C. Monge, J. Papillon and A. J. McTavish
Department of Medicine, Royal Victoria Hospital, McGill University, Montreal, Quebec, Canada.
In rat membranous nephropathy, complement C5b-9 induces glomerular epithelial cell (GEC) injury and proteinuria, which, in some models, is partially mediated by eicosanoids. By analogy, sublytic C5b-9 injures plasma membranes and releases arachidonic acid (AA) and eicosanoids in cultured rat GEC. In this study, we demonstrate that, in GEC, sublytic C5b-9 stably increased the activity of a high-molecular-mass cytosolic phospholipase A2 (PLA2), which we identified as "cPLA2." This increase was abolished with inhibitors of protein kinase C. C5b-9 did not affect low-molecular-mass membrane-associated or secretory PLA2 activities. In GEC that stably overexpress cPLA2 activity and protein (produced by transfection of cPLA2 cDNA), immunoblot analysis showed that sublytic C5b-9 induced a decreased mobility of cPLA2, consistent with cPLA2 phosphorylation. Incubation of cPLA2-transfected GEC with sublytic C5b-9 significantly increased production of free AA and prostaglandin E2, whereas, in control GEC, the C5b-9-induced changes in free AA and prostaglandin E2 were small. Furthermore, both C5b-9-dependent sublytic cytotoxicity and cytolysis were enhanced in GEC overexpressing cPLA2, compared with control cells. Thus C5b-9 increased cPLA2 activity, probably via phosphorylation involving a protein kinase C-dependent pathway. Phospholipid hydrolysis by cPLA2 resulted in release of substrate for eicosanoid synthesis and in enhancement of C5b-9-dependent GEC injury. Both processes may facilitate glomerular damage in membranous nephropathy.
This article has been cited by other articles:
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  D. Cohen, J. Papillon, L. Aoudjit, H. Li, A. V. Cybulsky, and T. Takano Role of calcium-independent phospholipase A2 in complement-mediated glomerular epithelial cell injury Am J Physiol Renal Physiol, March 1, 2008; 294(3): F469 - F479. [Abstract] [Full Text] [PDF]
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H. Zhang, A. V. Cybulsky, L. Aoudjit, J. Zhu, H. Li, N. Lamarche-Vane, and T. Takano Role of Rho-GTPases in complement-mediated glomerular epithelial cell injury Am J Physiol Renal Physiol, July 1, 2007; 293(1): F148 - F156. [Abstract] [Full Text] [PDF]
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L. Aoudjit, A. Potapov, and T. Takano Prostaglandin E2 promotes cell survival of glomerular epithelial cells via the EP4 receptor Am J Physiol Renal Physiol, June 1, 2006; 290(6): F1534 - F1542. [Abstract] [Full Text] [PDF]
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A. V. Cybulsky, R. J. Quigg, and D. J. Salant Experimental membranous nephropathy redux Am J Physiol Renal Physiol, October 1, 2005; 289(4): F660 - F671. [Abstract] [Full Text] [PDF]
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A. V. Cybulsky, T. Takano, J. Papillon, K. Bijian, and J. Guillemette Activation of the extracellular signal-regulated kinase by complement C5b-9 Am J Physiol Renal Physiol, September 1, 2005; 289(3): F593 - F603. [Abstract] [Full Text] [PDF]
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A. V. Cybulsky, T. Takano, J. Papillon, A. Khadir, K. Bijian, C.-C. Chien, C. E. Alpers, and H. Rabb Renal expression and activity of the germinal center kinase SK2 Am J Physiol Renal Physiol, January 1, 2004; 286(1): F16 - F25. [Abstract] [Full Text] [PDF]
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L. Aoudjit, M. Stanciu, H. Li, S. Lemay, and T. Takano p38 Mitogen-activated protein kinase protects glomerular epithelial cells from complement-mediated cell injury Am J Physiol Renal Physiol, October 1, 2003; 285(4): F765 - F774. [Abstract] [Full Text] [PDF]
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 T. Takano, A. V. Cybulsky, W. A. Cupples, D. O. Ajikobi, J. Papillon, and L. Aoudjit Inhibition of Cyclooxygenases Reduces Complement-Induced Glomerular Epithelial Cell Injury and Proteinuria in Passive Heymann Nephritis J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 240 - 249. [Abstract] [Full Text]
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 H. Peng, T. Takano, J. Papillon, K. Bijian, A. Khadir, and A. V. Cybulsky Complement Activates the c-Jun N-Terminal Kinase/Stress-Activated Protein Kinase in Glomerular Epithelial Cells J. Immunol., September 1, 2002; 169(5): 2594 - 2601. [Abstract] [Full Text] [PDF]
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 H. Yuan, E. Takeuchi, G. A. Taylor, M. McLaughlin, D. Brown, and D. J. Salant Nephrin Dissociates from Actin, and Its Expression Is Reduced in Early Experimental Membranous Nephropathy J. Am. Soc. Nephrol., April 1, 2002; 13(4): 946 - 956. [Abstract] [Full Text] [PDF]
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T. Takano, A. V. Cybulsky, X. Yang, and L. Aoudjit Complement C5b-9 induces cyclooxygenase-2 gene transcription in glomerular epithelial cells Am J Physiol Renal Physiol, November 1, 2001; 281(5): F841 - F850. [Abstract] [Full Text] [PDF]
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 T. Takano and A. V. Cybulsky Complement C5b-9-Mediated Arachidonic Acid Metabolism in Glomerular Epithelial Cells : Role of Cyclooxygenase-1 and -2 Am. J. Pathol., June 1, 2000; 156(6): 2091 - 2101. [Abstract] [Full Text] [PDF]
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A. V. Cybulsky, T. Takano, J. Papillon, and A. J. McTavish Complement C5b-9 Induces Receptor Tyrosine Kinase Transactivation in Glomerular Epithelial Cells Am. J. Pathol., November 1, 1999; 155(5): 1701 - 1711. [Abstract] [Full Text] [PDF]
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