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Chem Biol Interact. 2005 Sep 10;156(1):69-80.

Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel sulfate-induced human lymphocyte death in vitro.

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1
Human Toxicology Research Group (TOXHUM), Department of Environmental and Occupational Health, Faculty of Medicine, Université de Montréal, P.O. Box 6128, Main Station, Montréal, Que., Canada H3C 3J7.

Abstract

When isolated human lymphocytes were treated in vitro with various concentrations of nickel sulfate (NiSO4) (0-4 mM) at 37 degrees C for 4 h, both concentration- and time-dependent effects of NiSO4 on lymphocyte death were observed. Increased generation of hydrogen peroxide, depletion of both nonprotein and protein sulfhydryl contents, and lipid peroxidation were induced by NiSO4. NiSO4-induced lymphocyte death was significantly prevented by pre-treatment with either catalase, or dimethylthiourea/mannitol, or deferoxamine, or excess glutathione/N-acetylcysteine. Cotreatment with cyclosporin A (a specific inhibitor of mitochondrial membrane potential) not only inhibited NiSO4-induced mitochondrial membrane potential, but also significantly prevented Ni compound-induced lymphocyte death. NiSO4-induced lymphocyte death was also significantly prevented by modulating intracellular calcium fluxes using both Ca2+ channel blockers and intracellular Ca2+ antagonist. Thus, the mechanism of NiSO4-induced activation of lymphocyte death signalling pathways involves not only the excess generation of different types of oxidative stress but also NiSO4-induced loss of mitochondrial membrane potential and destabilization of cellular calcium homeostasis as well.

PMID:
16125158
DOI:
10.1016/j.cbi.2005.07.004
[Indexed for MEDLINE]
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