The molecular mechanisms by which nickel compounds cause immune cytotoxicity are far from understood. Our preliminary data suggested that nickel(II) induced apoptosis in Jurkat cells by mitochondrial pathway, specifically via mitochondrial membrane potential dissipation and antiapoptotic gene bcl-2 down-regulation. The main goal of this study was to further investigate the toxicity of nickel, especially the induction of reactive oxygen species (ROS) on immune cells, which finally induced apoptosis. Nickel was found to induce glutathione (GSH) depletion in a dose- and time-dependent manner. When Jurkat cells were preincubated with antioxidant N-acetylcysteine (NAC), apoptosis was inhibited distinctly, which suggested that ROS played an initial role in nickel immune toxicity. Heme oxygenase-1 (HO-1) and Nitric oxide (NO) which may play an important role in regulatory and protective processes in cells were assayed upon nickel treatment. A significant increase in HO-1 mRNA levels was detected in nickel treated cells. We confirmed that reduction of Nitrate levels in Jurkat cells was due to down-regulation of inducible nitric oxide synthase (iNOS), not endothelial nitric oxide synthase (eNOS). Expression changes of HO-1 and iNOS were markedly blocked when Jurkat cells were preincubated with NAC, suggesting that ROS resulted in HO-1 and iNOS dysfunction in Jurkat cells. We supposed that the immune toxicity of nickel(II) was mainly due to GSH depletion and finally led to apoptosis, probably via changing the expression levels of HO-1 and iNOS in human T lymphocytes.
- Nitric oxide