Cellular toxicity of cadmium ions and their detoxification by heavy metal-specific plant peptides, phytochelatins, expressed in mammalian cells

The apoptotic cell death of Jurkat cells due to Cd2+ toxicity was studied by fluorescence microscopic observation and DNA fragmentation assaying. It was suggested that the apoptotic response to Cd2+ was less clear than that to a typical apoptosis inducer, ultraviolet light (254 nm). Examination of MAP kinase phosphorylation (p38, JNKs, and c-Jun) due to Cd2+ toxicity indicated that the phosphorylation was very slowly activated (4 h after stimulation), while UV light could activate the phosphorylation immediately. Therefore, it was suggested that Cd2+ may not be a typical apoptosis inducer. Antioxidants [glutathione (GSH) and N-acetylcysteine (NAC)] could detoxify Cd2+, indicating that the toxicity is a kind of oxidative stress. The detoxification effect of antioxidants showed cooperation with Bcl-2, suggesting that Cd2+-treatment causes diversified toxic signals including oxidative stress. On the addition of a plant-specific peptide, phytochelatin [PC7, (gamma-Glu-Cys)(7)-Gly], to the medium, the detoxification of Cd2+ and cooperation with Bcl-2 were more intense than in the cases of GSH and NAC. Using an appropriate vector, a PC synthase gene was transferred from Arabidopsis thaliana to the Jurkat cell. The transfectant exhibited resistance to Cd2+ and production of plant-specific PC (PC2-6).