Caspase-independent commitment phase to apoptosis in activated blood T lymphocytes:: reversibility at low apoptotic insult
Caspase-independent commitment phase to apoptosis in activated blood T lymphocytes:: reversibility at low apoptotic insult
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DOI：
10.1182/blood.v96.3.1030.015k21_1030_1038
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发表时间：
2000-08-01
期刊：
影响因子：
20.3
通讯作者：
Senik, A
中科院分区：
文献类型：
--
作者：
Dumont, C;Dürrbach, A;Senik, A
很少有人知道的机制，程序性死亡触发T淋巴细胞的刺激，可以绕过半胱天冬酶激活。抗CDP单克隆抗体和星形孢菌素是这样的细胞凋亡诱导剂，因为它们在广谱半胱天冬酶抑制剂BOC-D. fetus和Z-VAD. fetus的存在下起作用。基于根据逐渐参与细胞凋亡过程的活化的血液T细胞的密度的分离，设计了一种系统，这允许定义由抗CD 2和星形孢菌素触发的半胱天冬酶依赖性和半胱天冬酶非依赖性致突变事件的序列。因此，定义了细胞凋亡的定型阶段，其完全不依赖于半胱天冬酶，并且其特征在于细胞体积损失、部分染色质浓缩和线粒体“凋亡诱导因子”（AIF）释放到胞质溶胶和细胞核中。定型细胞是存活的，显示出高的线粒体内跨膜电位（Δ Psim），并且缺乏大规模和寡核小体DNA片段化。AIF的线粒体释放是选择性的，因为细胞色素c保留在非常相同的细胞的线粒体中。细胞色素c的线粒体释放发生得较晚，在细胞凋亡的执行阶段开始时，与Δ Psim塌陷、聚（ADP-核糖）聚合酶切割和DNA片段化同时发生。如果刺激强度低且持续时间短，则该承诺阶段的细胞凋亡事件是可逆的。(C)2000年，美国血液学会。
Little is known about the mechanisms of programmed death triggered in T lymphocytes by stimuli that can bypass caspase activation. Anti-CDP monoclonal antibody and staurosporine are such apoptosis inducers because they operate in the presence of broad-spectrum caspase inhibitors BOC-D.fmk and Z-VAD.fmk, A system was devised, based on the isolation according to density of activated blood T cells progressively engaged in the apoptotic process, This allowed definition of a sequence of caspase-dependent and caspase-independent apoptogenic events that are triggered by anti-CD2 and staurosporine. Thus, a commitment phase to apoptosis was defined that is entirely caspase independent and that is characterized by cell volume loss, partial chromatin condensation, and release into the cytosol and the nucleus of mitochondrial "apoptosis-inducing factor" (AIF), Committed cells were viable, displayed a high mitochondrial inner transmembrane potential (Delta Psi m), and lacked large-scale and oligonucleosomal DNA fragmentation. Mitochondrial release of AIF was selective because cytochrome c was retained in mitochondria of the very same cells, Mitochondrial release of cytochrome c occurred later, at the onset of the execution phase of apoptosis, concurrently with Delta Psi m collapse, poly (ADP-ribose) polymerase cleavage, and DNA fragmentation. The apoptogenic events of this commitment phase are reversible if the strength of the stimulus is low and of short duration. (C) 2000 by The American Society of Hematology.