Characterization of calcineurin in human neutrophils: inhibitory effect of hydrogen peroxide on its enzyme activity and on NF-κB DNA binding
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Título: | Characterization of calcineurin in human neutrophils: inhibitory effect of hydrogen peroxide on its enzyme activity and on NF-κB DNA binding |
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Autor/es: | Carballo Álvarez, Modesto | Márquez, Gracia | Conde, Manuel | Martín-Nieto, José | Monteseirín Mateo, Javier | Conde Hernández, José | Pintado Sanjuan, Elizabeth | Sobrino Beneyto, Francisco |
Grupo/s de investigación o GITE: | Genética Humana y de Mamíferos |
Centro, Departamento o Servicio: | Universidad de Alicante. Departamento de Fisiología, Genética y Microbiología | Universidad de Sevilla. Departamento de Bioquímica Médica y Biología Molecular | Hospital Universitario Virgen Macarena. Servicio Regional de Inmunología y Alergia |
Palabras clave: | Calcineurin | Human neutrophils | Enzyme activity | Hydrogen peroxide |
Área/s de conocimiento: | Genética | Bioquímica y Biología Molecular |
Fecha de creación: | 18-ago-1998 |
Fecha de publicación: | 1-ene-1999 |
Editor: | American Society for Biochemistry and Molecular Biology |
Cita bibliográfica: | CARBALLO ÁLVAREZ, Modesto, et al. "Characterization of calcineurin in human neutrophils: inhibitory effect of hydrogen peroxide on its enzyme activity and on NF-κB DNA binding". Journal of Biological Chemistry. Vol. 274, No. 1 (Jan. 1999). ISSN 0021-9258, pp. 93-100 |
Resumen: | 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-κB 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-κB/Rel proteins in human neutrophils. These data indicate a role of peroxides in the modulation of calcineurin activity and that the H2O2-dependent NF-κB inactivation in neutrophils occurs in concert with inhibition of calcineurin. |
Patrocinador/es: | This work was supported in part by Fondo Investigaciones Sanitarias Grants 94/1484 and 97/1289 (to F. S.) and Grant 97/207 (to J. C.) and the Fundation of SEAIC of Spain. |
URI: | http://hdl.handle.net/10045/9722 |
ISSN: | 0021-9258 (Print) | 1083-351X (Online) |
DOI: | 10.1074/jbc.274.1.93 |
Idioma: | eng |
Tipo: | info:eu-repo/semantics/article |
Derechos: | This research was originally published in Journal of Biological Chemistry. Carballo Álvarez, Modesto, et al. Characterization of calcineurin in human neutrophils: inhibitory effect of hydrogen peroxide on its enzyme activity and on NF-κB DNA binding. Journal of Biological Chemistry. 1999. 274:93-100. © the American Society for Biochemistry and Molecular Biology |
Revisión científica: | si |
Aparece en las colecciones: | INV - GHM - Artículos de Revistas |
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