Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel subsulfide-induced human lymphocyte death in vitro.
When isolated human lymphocytes were treated in vitro either with various concentrations (0-2 mM) of soluble form of nickel subsulfide (Ni(3)S(2)) at 37 degrees C for 4 h or at various times (0-240 min), both concentration- and time-dependent effects of Ni(3)S(2) on lymphocyte death were observed. Increased generation of hydrogen peroxide (H(2)O(2)), and superoxide anion (O(2)(-)), lipid peroxidation and depletion of both nonprotein (NP-) and protein (P-) sulfhydryl (SH) contents were induced by 1 mM Ni(3)S(2). Ni(3)S(2)-induced lymphocyte death was significantly prevented by pre-treatment with either catalase (a H(2)O(2) scavenger), or superoxide dismutase (scavenger of O(2)(-) radical), or dimethylthiourea/mannitol (hydroxyl radical scavengers), or deferoxamine (iron-chelator), or glutathione/N-acetylcysteine. Co-treatment with cyclosporin A (a mitochondrial membrane potential' inhibitor) inhibited Ni(3)S(2)-induced disturbances in mitochondrial membrane potential, and significantly prevented Ni(3)S(2)-induced lymphocyte death. Ni(3)S(2)-induced lymphocyte death was also significantly prevented by modulating intracellular calcium fluxes using both Ca(2+) channel blockers and intracellular Ca(2+) antagonists. Thus, the mechanism of soluble Ni(3)S(2)-induced activation of lymphocyte death signalling pathways involves increasing generation of different types of oxidative stress, disturbances in mitochondrial membrane potential and cellular calcium homeostasis' destabilization.[1]References
- Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel subsulfide-induced human lymphocyte death in vitro. M'bemba-Meka, P., Lemieux, N., Chakrabarti, S.K. Sci. Total Environ. (2006) [Pubmed]
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