Hydrogen peroxide mediates activation of nuclear factor of activated T cells (NFAT) by nickel subsulfide

Citation
Cs. Huang et al., Hydrogen peroxide mediates activation of nuclear factor of activated T cells (NFAT) by nickel subsulfide, CANCER RES, 61(22), 2001, pp. 8051-8057
Citations number
46
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
61
Issue
22
Year of publication
2001
Pages
8051 - 8057
Database
ISI
SICI code
0008-5472(20011115)61:22<8051:HPMAON>2.0.ZU;2-1
Abstract
Nickel compounds induce cell transformation in cell culture models and tumo r formation in experimental animals. However, the molecular mechanisms by w hich nickel compounds induce tumors are not yet well understood. The presen t study found that exposure of cells to either Ni3S2 or NiCl2 could result in specific transactivation of nuclear factor of activated T cells (NFAT), although it did not show any activation of p53 or AP-1. Furthermore, nickel compounds were also able to cause generation of reactive oxygen species (R OS). The scavenging of nickel-induced H2O2 with N-acety-L-cyteine (a genera l antioxidant) or catalase, or the chelation of nickel with deferoxamine, r esulted in inhibition of NFAT activation. In contrast, pretreatment of cell s with sodium formate (an . OH radical scavenger) or superoxide dismutase ( an O . (-)(2) radical scavenger) did not show any inhibitory effects. These results demonstrate that nickel compounds are able to induce NFAT activati on, and that the mechanism of NFAT activation seems to be mediated by the g eneration of H2O2 by these metal compounds. This study should help us under stand the signal transduction pathways involved in carcinogenic effects of these nickel compounds.