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 Carballo, M. Articles by Sobrino, F. Search for Related Content PubMed PubMed Citation Articles by Carballo, M. Articles by Sobrino, F.

J Biol Chem, Vol. 274, Issue 1, 93-100, January 1, 1999

Characterization of Calcineurin in Human Neutrophils
INHIBITORY EFFECT OF HYDROGEN PEROXIDE ON ITS ENZYME ACTIVITY AND ON NF-B DNA BINDING

Modesto Carballo, Gracia Márquez, Manuel Conde, José Martín-Nieto, Javier Monteseirín^**, José Conde^**, Elizabeth Pintado, and Francisco Sobrino^**

From the  Departamento de Bioquímica Médica y Biología Molecular, Facultad de Medicina, ^** Departamento de Medicina, Servicio Regional de Inmunología y Alergia, Hospital Universitario Virgen Macarena, Universidad de Sevilla, 41009 Seville and  Departamento de Biotecnología, Campus Universitario San V. del Raspeig, Universidad de Alicante, Alicante, Spain

We describe here a specific calcineurin activity in neutrophil lysates, which is dependent on Ca²⁺, inhibited by trifluoroperazine, and insensitive to okadaic acid. Immunoblotting experiments using a specific antiserum recognized both the A and B chains of calcineurin. Neutrophils treated with cyclosporin A or FK 506 showed a dose-dependent inhibition of calcineurin activity. The effect of oxidant compounds on calcineurin activity was also investigated. Neutrophils treated with hydrogen peroxide (H₂O₂), where catalase was inhibited with aminotriazole, exhibited a specific inhibition of calcineurin activity. However, the addition of reducing agents to neutrophil extracts partially reversed the inhibition caused by H₂O₂. A similar inhibitory effect of H₂O₂ on calcineurin activity was observed to occur in isolated lymphocytes. This is the first demonstration that redox agents modulate calcineurin activity in a cellular system. In addition, electrophoretic mobility shift assays revealed that lipopolysaccharide-induced activation of NF-B in human neutrophils is inhibited by cell pretreatment with H₂O₂ in a dose-dependent manner. These data indicate that calcineurin activity regulates the functional activity of lipopolysaccharide-induced NF-B/Rel proteins in human neutrophils. These data indicate a role of peroxides in the modulation of calcineurin activity and that the H₂O₂-dependent NF-B inactivation in neutrophils occurs in concert with inhibition of calcineurin.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				Y. Zhang, D.-H. Lin, Z.-J. Wang, Y. Jin, B. Yang, and W.-H. Wang K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD Am J Physiol Cell Physiol, March 1, 2008; 294(3): C765 - C773. [Abstract] [Full Text] [PDF]

				R. El Bekay, G. Alba, M E. Reyes, P. Chacon, A. Vega, J. Martin-Nieto, J. Jimenez, E. Ramos, J. Olivan, E. Pintado, et al. Rac2 GTPase activation by angiotensin II is modulated by Ca2+/calcineurin and mitogen-activated protein kinases in human neutrophils J. Mol. Endocrinol., November 1, 2007; 39(5): 351 - 363. [Abstract] [Full Text] [PDF]

				J. Monteseirin, A. Vega, P. Chacon, M. J. Camacho, R. El Bekay, J. A. Asturias, A. Martinez, P. Guardia, R. Perez-Cano, and J. Conde Neutrophils as a Novel Source of Eosinophil Cationic Protein in IgE-Mediated Processes J. Immunol., August 15, 2007; 179(4): 2634 - 2641. [Abstract] [Full Text] [PDF]

				A. Vega, P. Chacon, J. Monteseirin, R. El Bekay, G. Alba, J. Martin-Nieto, and F. Sobrino Expression of the transcription factor NFAT2 in human neutrophils: IgE-dependent, Ca2+- and calcineurin-mediated NFAT2 activation J. Cell Sci., July 15, 2007; 120(14): 2328 - 2337. [Abstract] [Full Text] [PDF]

				A. Vega, P. Chacon, G. Alba, R. El Bekay, J. Monteseirin, J. Martin-Nieto, and F. Sobrino Modulation of IgE-dependent COX-2 gene expression by reactive oxygen species in human neutrophils J. Leukoc. Biol., July 1, 2006; 80(1): 152 - 163. [Abstract] [Full Text] [PDF]

				Y. Lu and L. M. Wahl Oxidative Stress Augments the Production of Matrix Metalloproteinase-1, Cyclooxygenase-2, and Prostaglandin E2 through Enhancement of NF-{kappa}B Activity in Lipopolysaccharide-Activated Human Primary Monocytes J. Immunol., October 15, 2005; 175(8): 5423 - 5429. [Abstract] [Full Text] [PDF]

				J. Monteseirin, P. Chacon, A. Vega, R. El Bekay, M. Alvarez, G. Alba, M. Conde, J. Jimenez, J. A. Asturias, A. Martinez, et al. Human neutrophils synthesize IL-8 in an IgE-mediated activation J. Leukoc. Biol., September 1, 2004; 76(3): 692 - 700. [Abstract] [Full Text] [PDF]

				M. Alvarez-Maqueda, R. E. Bekay, G. Alba, J. Monteseirin, P. Chacon, A. Vega, J. Martin-Nieto, F. J. Bedoya, E. Pintado, and F. Sobrino 15-Deoxy-{Delta}12,14-prostaglandin J2 Induces Heme Oxygenase-1 Gene Expression in a Reactive Oxygen Species-dependent Manner in Human Lymphocytes J. Biol. Chem., May 21, 2004; 279(21): 21929 - 21937. [Abstract] [Full Text] [PDF]

				M. M. Monick, L. Samavati, N. S. Butler, M. Mohning, L. S. Powers, T. Yarovinsky, D. R. Spitz, and G. W. Hunninghake Intracellular Thiols Contribute to Th2 Function via a Positive Role in IL-4 Production J. Immunol., November 15, 2003; 171(10): 5107 - 5115. [Abstract] [Full Text] [PDF]

				S. Iho, Y. Tanaka, R. Takauji, C. Kobayashi, I. Muramatsu, H. Iwasaki, K. Nakamura, Y. Sasaki, K. Nakao, and T. Takahashi Nicotine induces human neutrophils to produce IL-8 through the generation of peroxynitrite and subsequent activation of NF-{kappa}B J. Leukoc. Biol., November 1, 2003; 74(5): 942 - 951. [Abstract] [Full Text] [PDF]

				R. El Bekay, M. Alvarez, J. Monteseirin, G. Alba, P. Chacon, A. Vega, J. Martin-Nieto, J. Jimenez, E. Pintado, F. J. Bedoya, et al. Oxidative stress is a critical mediator of the angiotensin II signal in human neutrophils: involvement of mitogen-activated protein kinase, calcineurin, and the transcription factor NF-{kappa}B Blood, July 15, 2003; 102(2): 662 - 671. [Abstract] [Full Text] [PDF]

				C. J. Howe, M. M. LaHair, J. A. Maxwell, J. T. Lee, P. J. Robinson, O. Rodriguez-Mora, J. A. McCubrey, and R. A. Franklin Participation of the Calcium/Calmodulin-dependent Kinases in Hydrogen Peroxide-induced Ikappa B Phosphorylation in Human T Lymphocytes J. Biol. Chem., August 16, 2002; 277(34): 30469 - 30476. [Abstract] [Full Text] [PDF]

				L. Samavati, M. M. Monick, S. Sanlioglu, G. R. Buettner, L. W. Oberley, and G. W. Hunninghake Mitochondrial KATP channel openers activate the ERK kinase by an oxidant-dependent mechanism Am J Physiol Cell Physiol, July 1, 2002; 283(1): C273 - C281. [Abstract] [Full Text] [PDF]

				D. Namgaladze, H. W. Hofer, and V. Ullrich Redox Control of Calcineurin by Targeting the Binuclear Fe2+-Zn2+ Center at the Enzyme Active Site J. Biol. Chem., February 15, 2002; 277(8): 5962 - 5969. [Abstract] [Full Text] [PDF]

				R. El Bekay, M. Alvarez, M. Carballo, J. Martin-Nieto, J. Monteseirin, E. Pintado, F. J. Bedoya, and F. Sobrino Activation of phagocytic cell NADPH oxidase by norfloxacin: a potential mechanism to explain its bactericidal action J. Leukoc. Biol., February 1, 2002; 71(2): 255 - 261. [Abstract] [Full Text] [PDF]

				R. Caruso, N. Perico, D. Cattaneo, G. Piccinini, S. Bonazzola, G. Remuzzi, and F. Gaspari Whole-Blood Calcineurin Activity Is Not Predicted by Cyclosporine Blood Concentration in Renal Transplant Recipients Clin. Chem., September 1, 2001; 47(9): 1679 - 1687. [Abstract] [Full Text] [PDF]

				H. Holschermann, C. Rascher, C. Oelschlager, G. Stapfer, A. Langenstein, A. Staubitz, U. Maus, H. Tillmanns, H. Bang, and W. Haberbosch Opposite Regulation of Tissue Factor Expression by Calcineurin in Monocytes and Endothelial Cells J. Immunol., June 15, 2001; 166(12): 7112 - 7120. [Abstract] [Full Text] [PDF]

				F. Rusnak and P. Mertz Calcineurin: Form and Function Physiol Rev, October 1, 2000; 80(4): 1483 - 1521. [Abstract] [Full Text] [PDF]

				M. Carballo, M. Conde, R. El Bekay, J. Martin-Nieto, M. J. Camacho, J. Monteseirin, J. Conde, F. J. Bedoya, and F. Sobrino Oxidative Stress Triggers STAT3 Tyrosine Phosphorylation and Nuclear Translocation in Human Lymphocytes J. Biol. Chem., June 18, 1999; 274(25): 17580 - 17586. [Abstract] [Full Text] [PDF]

				V. See and J.-P. Loeffler Oxidative Stress Induces Neuronal Death by Recruiting a Protease and Phosphatase-gated Mechanism J. Biol. Chem., September 7, 2001; 276(37): 35049 - 35059. [Abstract] [Full Text] [PDF]