Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel sulfate-induced human lymphocyte death in vitro
Role of oxidative stress, mitochondrial membrane potential, and calcium homeostasis in nickel sulfate-induced human lymphocyte death in vitro
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DOI：
10.1016/j.cbi.2005.07.004
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发表时间：
2005-09-10
影响因子：
5.1
通讯作者：
Chakrabarti, SK
中科院分区：
文献类型：
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作者：
M'Bemba-Meka, P;Lemieux, N;Chakrabarti, SK
当分离的人淋巴细胞在体外处理不同浓度的硫酸镍（NiSO 4）（0-4 mM）在37 ℃ 4小时，浓度和时间依赖性的影响NiSO 4对淋巴细胞死亡进行了观察。过氧化氢的产生增加，消耗非蛋白质和蛋白质巯基含量，和脂质过氧化诱导硫酸镍。NiSO 4诱导的淋巴细胞死亡显着防止预处理与过氧化氢酶，或二甲基硫乙醇/甘露醇，或去铁胺，或过量的谷胱甘肽/N-乙酰半胱氨酸。与线粒体膜电位特异性抑制剂环孢菌素A（cyclosporin A）共处理不仅能抑制NiSO_4诱导的线粒体膜电位，而且能显著阻止Ni化合物诱导的淋巴细胞死亡。NiSO 4诱导的淋巴细胞死亡也显着防止通过调节细胞内钙流使用两个Ca 2+通道阻滞剂和细胞内Ca 2+拮抗剂。因此，NiSO 4诱导的淋巴细胞死亡信号通路激活的机制不仅涉及不同类型的氧化应激的过度产生，而且还涉及NiSO 4诱导的线粒体膜电位的丧失和细胞钙稳态的不稳定。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
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 dimethylth-iourea/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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.