Vanadium-induced nuclear factor of activated T cells activation through hydrogen peroxide

Citation
Cs. Huang et al., Vanadium-induced nuclear factor of activated T cells activation through hydrogen peroxide, J BIOL CHEM, 276(25), 2001, pp. 22397-22403
Citations number
62
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Biochemistry & Biophysics
Journal title
JOURNAL OF BIOLOGICAL CHEMISTRY
ISSN journal
0021-9258 → ACNP
Volume
276
Issue
25
Year of publication
2001
Pages
22397 - 22403
Database
ISI
SICI code
0021-9258(20010622)276:25<22397:VNFOAT>2.0.ZU;2-B
Abstract
The present study investigated the role of reactive oxygen species (ROS) in activation of nuclear factor of activated T cells (NFAT), a pivotal transc ription factor responsible for regulation of cytokines, by vanadium in mous e embryo fibroblast PW cells or mouse epidermal Cl 41 cells. Exposure of ce lls to vanadium led to the transactivation of NFAT in a time- and dose-depe ndent manner. Scavenging of vanadium-induced H2O2 with Nacety-L-cyteine (a general antioxidant) or catalase (a specific H2O2 inhibitor) or the chelati on of vanadate with deferoxamine, resulted in inhibition of NFAT activation . In contrast, an increase in H2O2 generation by the addition of superoxide dismutase or NADPH enhanced vanadium-induced NEAT activation. This vanadat e-mediated H2O2 generation was verified by both electron spin resonance and fluorescence staining assay. These results demonstrate that H2O2 plays an important role in vanadium-induced NFAT transactivation in two different ce ll types. Furthermore, pretreatment of cells with nifedipine, a calcium cha nnel blocker, inhibited vanadium-induced NFAT activation, whereas A23187 an d ionomycin, two calcium ionophores, had synergistic effects with vanadium for NFAT induction, Incubation of cells with cyclosporin A (CsA), a pharmac ological inhibitor of the phosphatase calcineurin, blocked vanadium-induced NFAT activation. Ah data show that vanadium induces NFAT activation not on ly through a calcium-dependent and CsA-sensitive pathway but also involved H2O2 generation, suggesting that H2O2 may be involved in activation of calc ium-calcineurin pathways for NFAT activation caused by vanadium exposure.