Activated T Cells (NFAT) by Nickel Subsulfide Hydrogen Peroxide Mediates Activation of Nuclear Factor of Updated Version

Nickel compounds induce cell transformation in cell culture models and tumor formation in experimental animals. However, the molecular mechanisms by which nickel compounds induce tumors are not yet well understood. The present 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 (ROS). The scavenging of nickel-induced H2O2 with N-acety-L-cyteine (a general antioxidant) or catalase, or the chelation of nickel with deferoxamine, resulted in inhibition of NFAT activation. In contrast, pretreatment of cells with sodium formate (an OH radical scavenger) or superoxide dismutase (an O2 . radical scavenger) did not show any inhibitory effects. These results demonstrate that nickel compounds are able to induce NFAT activation, and that the mechanism of NFAT activation seems to be mediated by the generation of H2O2 by these metal compounds. This study should help us understand the signal transduction pathways involved in carcinogenic effects of these nickel compounds.