2007 JASN IMPACT FACTOR 7.111	HOME   AUTHOR INFO   EDITORIAL BOARD   SUBSCRIBE   FEEDBACK   ALERTS   HELP
advanced	CURRENT ISSUE	ARCHIVES	JASN Express	ONLINE SUBMISSION

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 Krepinsky, J. C. Articles by Scholey, J. W. Search for Related Content PubMed PubMed Citation Articles by Krepinsky, J. C. Articles by Scholey, J. W.

Nitric Oxide Inhibits Stretch-Induced MAPK Activation in Mesangial Cells Through RhoA Inactivation

Joan C. Krepinsky^*, Alistair J. Ingram, Damu Tang, Dongcheng Wu, Lieqi Liu and James W. Scholey^*

*Department of Medicine, University of Toronto, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada.

Correspondence to Dr. Joan C. Krepinsky, 708-25 Charlton Ave. East, Hamilton, ON, L8N 1Y2, Canada. Phone: 905-522-1155 ext. 3155; Fax: 905-521-6153;

ABSTRACT. Glomerular capillary hypertension is an important determinant of glomerulosclerosis in rats with subtotal renal ablation. Dietary supplementation with L-arginine increases renal nitric oxide (NO) production and limits glomerular injury in this model, and early benefits are seen without altered glomerular capillary pressure. In an in vitro model of hemodynamically mediated signaling, the authors have reported that subjecting MC to cyclic stretch/relaxation activates the mitogen-activated protein kinase p42/44 (Erk) cascade and that NO and cyclic GMP abrogate stretch-induced Erk activation by inducing actin cytoskeletal disassembly. The actin cytoskeleton is regulated by the Rho family of GTPases, including RhoA; therefore, the authors examined the role of RhoA in stretch-induced Erk activation and as an NO target. In primary rat MC subjected to cyclic mechanical strain, RhoA activity was maximally increased (2.4-fold) after 1 min of stretch, and Erk activation temporally followed. The Rho-kinase inhibitor Y-27632 attenuated Erk activation in a dose-dependent manner and prevented stretch-induced actin stress fiber formation. The NO donors S-nitroso-N-acetylpenicillamine and cGMP both inhibited stretch-induced RhoA and Erk activation and stress fiber formation. Infection of MC with the RhoA mutant RhoA-Ala188, which is resistant to NO-dependent phosphorylation, abrogated the effects of NO and cGMP on stretch-induced Erk activation and stress fiber formation. The authors conclude that the early activation of RhoA is essential for stretch-induced actin stress fiber formation and Erk activation in MC, events which are prevented by NO and cGMP through their action on RhoA. Inhibition of RhoA may thus be a new approach to the prevention of hemodynamically mediated glomerular injury. E-mail: krepinj@mcmaster.ca

This article has been cited by other articles:

				F. Peng, B. Zhang, D. Wu, A. J. Ingram, B. Gao, and J. C. Krepinsky TGF{beta}-induced RhoA activation and fibronectin production in mesangial cells require caveolae Am J Physiol Renal Physiol, July 1, 2008; 295(1): F153 - F164. [Abstract] [Full Text] [PDF]

				F. Peng, D. Wu, B. Gao, A. J. Ingram, B. Zhang, K. Chorneyko, R. McKenzie, and J. C. Krepinsky RhoA/Rho-Kinase Contribute to the Pathogenesis of Diabetic Renal Disease Diabetes, June 1, 2008; 57(6): 1683 - 1692. [Abstract] [Full Text] [PDF]

				B. Wojciak-Stothard, B. Torondel, L. Y. F. Tsang, I. Fleming, B. Fisslthaler, J. M. Leiper, and P. Vallance The ADMA/DDAH pathway is a critical regulator of endothelial cell motility J. Cell Sci., March 15, 2007; 120(6): 929 - 942. [Abstract] [Full Text] [PDF]

				B. S. Zuckerbraun, D. A. Stoyanovsky, R. Sengupta, R. A. Shapiro, B. A. Ozanich, J. Rao, J. E. Barbato, and E. Tzeng Nitric oxide-induced inhibition of smooth muscle cell proliferation involves S-nitrosation and inactivation of RhoA Am J Physiol Cell Physiol, February 1, 2007; 292(2): C824 - C831. [Abstract] [Full Text] [PDF]

				F. Peng, D. Wu, A. J. Ingram, B. Zhang, B. Gao, and J. C. Krepinsky RhoA Activation in Mesangial Cells by Mechanical Strain Depends on Caveolae and Caveolin-1 Interaction J. Am. Soc. Nephrol., January 1, 2007; 18(1): 189 - 198. [Abstract] [Full Text] [PDF]

				C. K. Fujihara, C. R. Sena, D. M. A. C. Malheiros, A. L. Mattar, and R. Zatz Short-term nitric oxide inhibition induces progressive nephropathy after regression of initial renal injury Am J Physiol Renal Physiol, March 1, 2006; 290(3): F632 - F640. [Abstract] [Full Text] [PDF]

				J. Ziembicki, R. Tandon, J. R. Schelling, J. R. Sedor, R. T. Miller, and C. Huang Mechanical force-activated phospholipase D is mediated by G{alpha}12/13-Rho and calmodulin-dependent kinase in renal epithelial cells Am J Physiol Renal Physiol, October 1, 2005; 289(4): F826 - F834. [Abstract] [Full Text] [PDF]

				J. C. Krepinsky, Y. Li, Y. Chang, L. Liu, F. Peng, D. Wu, D. Tang, J. Scholey, and A. J. Ingram Akt Mediates Mechanical Strain-Induced Collagen Production by Mesangial Cells J. Am. Soc. Nephrol., June 1, 2005; 16(6): 1661 - 1672. [Abstract] [Full Text] [PDF]

				D. Xiao, L. D. Longo, and L. Zhang {alpha}1-Adrenoceptor-mediated phosphorylation of MYPT-1 and CPI-17 in the uterine artery: role of ERK/PKC Am J Physiol Heart Circ Physiol, June 1, 2005; 288(6): H2828 - H2835. [Abstract] [Full Text] [PDF]

				T. M. Seasholtz and J. H. Brown RHO SIGNALING in Vascular Diseases Mol. Interv., December 1, 2004; 4(6): 348 - 357. [Abstract] [Full Text] [PDF]

				X. Zhu, A. M. Herzenberg, M. Eskandarian, G. F. Maguire, J. W. Scholey, P. W. Connelly, and D. S. Ng A Novel in Vivo Lecithin-Cholesterol Acyltransferase (LCAT)-Deficient Mouse Expressing Predominantly LpX Is Associated with Spontaneous Glomerulopathy Am. J. Pathol., October 1, 2004; 165(4): 1269 - 1278. [Abstract] [Full Text] [PDF]

				L. Ling and P. E. Lobie RhoA/ROCK Activation by Growth Hormone Abrogates p300/Histone Deacetylase 6 Repression of Stat5-mediated Transcription J. Biol. Chem., July 30, 2004; 279(31): 32737 - 32750. [Abstract] [Full Text] [PDF]

Copyright © 2008 by the American Society of Nephrology. Online ISSN: 1533-3450 Print ISSN: 1046-6673