High susceptibility of activated lymphocytes to oxidative stress-induced cell death
High susceptibility of activated lymphocytes to oxidative stress-induced cell death
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DOI：
10.1590/s0001-37652008000100009
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发表时间：
2008-03-01
期刊：
影响因子：
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通讯作者：
Vercesi, Anibal E.
中科院分区：
文献类型：
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作者：
Degasperi, Giovanna R.;Castilho, Roger F.;Vercesi, Anibal E.
本研究提供的证据表明，活化脾淋巴细胞从步行者256荷瘤大鼠比对照组更容易叔丁基氢过氧化物（t-BOOH）诱导的坏死细胞死亡在体外。铁螯合剂和抗氧化剂去铁胺、细胞内钙螯合剂RAPTA、L型钙通道拮抗剂硝苯地平或线粒体通透性转换抑制剂环孢菌素A，但不是钙调磷酸酶抑制剂FK-506，使对照和活化淋巴细胞对t-BOOH的毒性作用具有同等的抗性。在t-BOOH存在下孵育活化的淋巴细胞导致线粒体膜电位的环孢菌素A敏感性降低。这些结果表明，较高的胞浆Ca 2+水平在活化的淋巴细胞增加其敏感性氧化应激诱导的细胞死亡的机制，涉及线粒体通透性转换的参与。
The present study provides evidence that activated spleen lymphocytes from Walker 256 tumor bearing rats are more susceptible than controls to tert-butyl hydroperoxide (t-BOOH)-induced necrotic cell death in vitro. The iron chelator and antioxidant deferoxamine, the intracellular Ca2+ chelator RAPTA, the L-type Ca2+ channel antagonist nifedipine or the mitochondrial permeability transition inhibitor cyclosporin A, but not the calcineurin inhibitor FK-506, render control and activated lymphocytes equally resistant to the toxic effects of t-BOOH. Incubation of activated lymphocytes in the presence of t-BOOH resulted in a cyclosporin A-sensitive decrease in mitochondrial membrane potential. These results indicate that the higher cytosolic Ca2+ level in activated lymphocytes increases their susceptibility to oxidative stress-induced cell death in a mechanism involving the participation of mitochondrial permeability transition.