ENDOGENOUS ENDONUCLEASE-INDUCED DNA FRAGMENTATION - AN EARLY EVENT IN CELL-MEDIATED CYTOLYSIS
ENDOGENOUS ENDONUCLEASE-INDUCED DNA FRAGMENTATION - AN EARLY EVENT IN CELL-MEDIATED CYTOLYSIS
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DOI：
10.1073/pnas.80.20.6361
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发表时间：
1983-01-01
期刊：
影响因子：
--
通讯作者：
COHEN, JJ
中科院分区：
文献类型：
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作者：
DUKE, RC;CHERVENAK, R;COHEN, JJ
在靶细胞[小鼠肥大细胞瘤P815，伴刀豆球蛋白A刺激的淋巴母细胞]暴露于细胞毒性T淋巴细胞的几分钟内，它们的核DNA开始断裂。这种现象先于51 Cr释放至少一个小时。DNA片段化仅在使用适当致敏的细胞毒性T细胞时发生，并且不仅仅是细胞死亡的结果，因为通过加热、冷冻/解冻或用抗体和补体裂解杀死靶细胞不会产生DNa片段。靶细胞DNA的琼脂糖凝胶电泳显示约200个碱基对亚基的离散倍数，表明片段化是特定核酸内切酶激活的结果。在糖皮质激素诱导的小鼠胸腺细胞杀伤过程中观察到类似的DNA片段模式。在这种情况下，核酸内切酶被锌离子抑制，我们发现，锌离子也抑制DNA片段化和51铬释放诱导的细胞毒性T细胞，这表明一个最终的共同的生化途径两种类型的细胞死亡。
Within minutes of exposure of target cells [mouse mastocytoma P815, concanavalin A-stimulated lymphoblasts] to cytotoxic T lymphocytes, their nuclear DNA begins to be fragmented. This phenomenon precedes 51Cr release by at least an hour. DNA fragmentation occurs only when appropriately sensitized cytotoxic T cells are used and is not merely a result of cell death because killing of target cells by heating, freeze/thawing, or lysing with antibody and complement did not yield DNa fragments. Agarose gel electrophoresis of target cell DNA showed discrete multiples of an approximately 200-base-pair subunit, suggesting that fragmentation was the result of activation of a specific endonuclease. A similar pattern of DNA fragments is observed during glucocorticoid-induced killing of mouse thymocytes. The endonuclease in that case is inhibited by Zn ions, and we find that Zn2+ also inhibits DNA fragmentation and 51Cr release induced by cytotoxic T cells, suggesting a final common biochemical pathway for both types of cell death.