INTRACELLULAR CA2+ SIGNALS ACTIVATE APOPTOSIS IN THYMOCYTES - STUDIES USING THE CA2+-ATPASE INHIBITOR THAPSIGARGIN

被引:248
作者
JIANG, S [1 ]
CHOW, SC [1 ]
NICOTERA, P [1 ]
ORRENIUS, S [1 ]
机构
[1] KAROLINSKA INST, INST ENVIRONM MED, DIV TOXICOL, S-17177 STOCKHOLM, SWEDEN
关键词
D O I
10.1006/excr.1994.1121
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The endoplasmic reticular Ca2+-ATPase inhibitor, thapsigargin, was used to study the role of an increase in cytosolic free calcium concentration ([Ca2+](i)) as a signal for the activation of thymocyte apoptosis. Treatment of rat thymocytes with thapsigargin resulted in an early sustained increase in [Ca2+](i) followed by extensive DNA fragmentation. Agarose gel electrophoresis revealed that the pattern of DNA fragments was typical of endonuclease-mediated internucleosomal cleavage. In addition, confocal,microscopy studies showed the formation of apoptotic nuclei in thapsigargin-treated thymocytes. The concentrations of thapsigargin required to induce DNA fragmentation and [Ca2+](i) increase in thymocytes were identical and so were the kinetics of thapsigargin-induced DNA fragmentation and formation of apoptotic nuclei. The lowest concentration of
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页码:84 / 92
页数:9
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