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 DÍAZ-CAZORLA, M. Articles by LAMAS, S. Search for Related Content PubMed PubMed Citation Articles by DÍAZ-CAZORLA, M. Articles by LAMAS, S.

Dual Effect of Nitric Oxide Donors on Cyclooxygenase-2 Expression in Human Mesangial Cells

Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas and Instituto "Reina Sofía" de Investigaciones Nefrológicas, C.S.I.C., Velázquez, Madrid, Spain.

Correspondence to Dr. Dolores Pérez-Sala or Dr. Santiago Lamas, Departamento de Estructura y Función de Proteínas, Centro de Investigaciones Biológicas, C.S.I.C., Velázquez, 144, 28006 Madrid, Spain. Phone: 34 91 5611800; Fax: 34 91 5627518; E-mail: lperezsala{at}fresno.csic.es or slamas{at}fresno.csic.es

Abstract. Nitric oxide (NO) is emerging as a key regulator of gene expression, capable of playing either positive or negative roles. The results of this study indicate that NO exerts a dual effect on cyclooxygenase-2 (COX-2) expression in human mesangial cells (HMC). Treatment of HMC with NO synthase inhibitors attenuated interleukin-1ß (IL-1ß)/tumor necrosis factor- (TNF-)-elicited COX-2 protein and mRNA expression, suggesting a positive role of endogenous NO on COX-2 induction. However, NO donors (sodium nitroprusside [SNP] and S-nitroso-N-acetylpenicillamine [SNAP]) amplified cytokine-elicited COX-2 expression at early time points of treatment (up to 8 h for mRNA and up to 24 h for protein expression), but were inhibitory at later times. Oligonucleotide decoy experiments confirmed the importance of nuclear factor B (NF-B) activation for COX-2 induction by IL-1ß/TNF-. Treatment with N^G-nitro-L-arginine methyl ester (L-NAME) did not affect initial activation of NF-B by IL-1ß/TNF-, but unveiled an inhibitory effect of NO generation on NF-B activity after 4 h. In HMC supplemented with SNP, cytokine-induced NF-B activation was potentiated at early times of induction (5 to 15 min), but inhibited at later times (1 to 4 h), suggesting a dual effect of NO donors on NF-B activation. Interestingly, IB protein levels followed a reciprocal pattern of expression: IB levels were lower at early times of induction in NO donor-supplemented cells; however, after 1 h of treatment, IB levels became higher than in cells treated only with cytokines. In the presence of SNP, cytokine-elicited IB mRNA induction was initially delayed, but was amplified at later times. These changes in IB expression could contribute to the dual effects of NO donors on NF-B activation and COX-2 expression in HMC.

This article has been cited by other articles:

				V. Mollace, C. Muscoli, E. Masini, S. Cuzzocrea, and D. Salvemini Modulation of Prostaglandin Biosynthesis by Nitric Oxide and Nitric Oxide Donors Pharmacol. Rev., June 1, 2005; 57(2): 217 - 252. [Abstract] [Full Text] [PDF]

				J. Yao, N. Hiramatsu, Y. Zhu, T. Morioka, M. Takeda, T. Oite, and M. Kitamura Nitric Oxide-Mediated Regulation of Connexin43 Expression and Gap Junctional Intercellular Communication in Mesangial Cells J. Am. Soc. Nephrol., January 1, 2005; 16(1): 58 - 67. [Abstract] [Full Text] [PDF]

				K.-S. Chun, H.-H. Cha, J.-W. Shin, H.-K. Na, K.-K. Park, W.-Y. Chung, and Y.-J. Surh Nitric oxide induces expression of cyclooxygenase-2 in mouse skin through activation of NF-{kappa}B Carcinogenesis, March 1, 2004; 25(3): 445 - 454. [Abstract] [Full Text] [PDF]

				D. Perez-Sala, E. Cernuda-Morollon, and F. J. Canada Molecular Basis for the Direct Inhibition of AP-1 DNA Binding by 15-Deoxy-{Delta}12,14-prostaglandin J2 J. Biol. Chem., December 19, 2003; 278(51): 51251 - 51260. [Abstract] [Full Text] [PDF]

				R. B. Pilz and D. E. Casteel Regulation of Gene Expression by Cyclic GMP Circ. Res., November 28, 2003; 93(11): 1034 - 1046. [Abstract] [Full Text] [PDF]

				F. Roig, M. T. Llinas, R. Lopez, and F. J. Salazar Role of Cyclooxygenase-2 in the Prolonged Regulation of Renal Function Hypertension, November 1, 2002; 40(5): 721 - 728. [Abstract] [Full Text] [PDF]

				E. Cernuda-Morollon, F. Rodriguez-Pascual, P. Klatt, S. Lamas, and D. Perez-Sala PPAR Agonists Amplify iNOS Expression While Inhibiting NF-{kappa}B: Implications for Mesangial Cell Activation by Cytokines J. Am. Soc. Nephrol., September 1, 2002; 13(9): 2223 - 2231. [Abstract] [Full Text] [PDF]

				D. W. Porter, L. Millecchia, V. A. Robinson, A. Hubbs, P. Willard, D. Pack, D. Ramsey, J. McLaurin, A. Khan, D. Landsittel, et al. Enhanced nitric oxide and reactive oxygen species production and damage after inhalation of silica Am J Physiol Lung Cell Mol Physiol, August 1, 2002; 283(2): L485 - L493. [Abstract] [Full Text] [PDF]

				L. Buschhausen, S. Seibold, O. Gross, T. Matthaeus, M. Weber, and E. Schulze-Lohoff Regulation of mesangial cell function by vasodilatory signaling molecules Cardiovasc Res, August 15, 2001; 51(3): 463 - 469. [Abstract] [Full Text] [PDF]

				G. K. RANGAN, Y. WANG, and D. C. H. HARRIS Pharmacologic Modulators of Nitric Oxide Exacerbate Tubulointerstitial Inflammation in Proteinuric Rats J. Am. Soc. Nephrol., August 1, 2001; 12(8): 1696 - 1705. [Abstract] [Full Text] [PDF]

				L. Connelly, M. Palacios-Callender, C. Ameixa, S. Moncada, and A. J. Hobbs Biphasic Regulation of NF-{{kappa}}B Activity Underlies the Pro- and Anti-Inflammatory Actions of Nitric Oxide J. Immunol., March 15, 2001; 166(6): 3873 - 3881. [Abstract] [Full Text] [PDF]

				D. Perez-Sala, E. Cernuda-Morollon, M. Diaz-Cazorla, F. Rodriguez-Pascual, and S. Lamas Posttranscriptional regulation of human iNOS by the NO/cGMP pathway Am J Physiol Renal Physiol, March 1, 2001; 280(3): F466 - F473. [Abstract] [Full Text] [PDF]

				R. Clancy, B. Varenika, W. Huang, L. Ballou, M. Attur, A. R. Amin, and S. B. Abramson Nitric Oxide Synthase/COX Cross-Talk: Nitric Oxide Activates COX-1 But Inhibits COX-2-Derived Prostaglandin Production J. Immunol., August 1, 2000; 165(3): 1582 - 1587. [Abstract] [Full Text] [PDF]

				L. Sandirasegarane, R. Charles, N. Bourbon, and M. Kester NO regulates PDGF-induced activation of PKB but not ERK in A7r5 cells: implications for vascular growth arrest Am J Physiol Cell Physiol, July 1, 2000; 279(1): C225 - C235. [Abstract] [Full Text] [PDF]

				H.-F. Cheng, J.-L. Wang, M.-Z. Zhang, James. A. McKanna, and R. C. Harris Nitric oxide regulates renal cortical cyclooxygenase-2 expression Am J Physiol Renal Physiol, July 1, 2000; 279(1): F122 - F129. [Abstract] [Full Text] [PDF]

				D. J. Wadleigh, S. T. Reddy, E. Kopp, S. Ghosh, and H. R. Herschman Transcriptional Activation of the Cyclooxygenase-2 Gene in Endotoxin-treated RAW 264.7 Macrophages J. Biol. Chem., February 25, 2000; 275(9): 6259 - 6266. [Abstract] [Full Text] [PDF]

				E. Cernuda-Morollon, E. Pineda-Molina, F. J. Canada, and D. Perez-Sala 15-Deoxy-Delta 12,14-prostaglandin J2 Inhibition of NF-kappa B-DNA Binding through Covalent Modification of the p50 Subunit J. Biol. Chem., September 14, 2001; 276(38): 35530 - 35536. [Abstract] [Full Text] [PDF]

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