Programmed cell death in heterokaryons. A study of the transfer of apoptosis between nuclei.

Programmed cell death in heterokaryons. A study of the transfer of apoptosis between nuclei.
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异核体中的程序性细胞死亡。

DOI:
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发表时间:
1992
影响因子:
6
通讯作者:
R. Youle
R. Youle
中科院分区:
医学2区
文献类型:
--
作者:
B. Dipasquale;R. Youle

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经历由地塞米松诱导的凋亡的胸腺细胞在诺马斯基光学下显示出核折射率的变化,这与核小体间 DNA 降解精确相关,并且被放线菌酮所阻止。当检查胸腺细胞和9L或NIH3T3细胞之间的异核体时,异核体中99.75%的细胞核遵循亲本细胞的原始且独特的命运特征。胸腺细胞核继续发生细胞凋亡,而异核体中的 9L 和 NIH3T3 细胞核在凝胶上没有显示凋亡的形态变化或任何 DNA 裂解,并且保持活力和有丝分裂。放线菌酮阻止异核体中胸腺细胞核凋亡的诱导。在异核体中经历程序性细胞死亡的过量至多七个胸腺细胞核并未检测到对 9L 细胞核的损害,并且过量的 6 个 9L 细胞核也不能保护胸腺细胞核免于凋亡。提出的模型指出程序性细胞死亡是由致死基因产物的从头合成引起的,这很难与这些发现相一致。在用皮质类固醇诱导细胞凋亡之前,胸腺细胞核中存在一种细胞类型特异性活性,并且无法在细胞核之间扩散,这似乎是造成 DNA 断裂的原因。这些结果还表明,核崩解是胸腺细胞死亡的触发因素,而不是由于另一种机制导致细胞死亡的结果。
Thymocytes undergoing apoptosis induced by dexamethasone showed nuclear refractivity changes under Nomarski optics that correlated precisely with internucleosomal DNA degradation and was prevented by cycloheximide. When heterokaryons between thymocytes and 9L or NIH3T3 cells were examined, 99.75% of the nuclei in heterokaryons followed the original and distinct fate characteristic of the parental cells. Thymocyte nuclei proceeded to undergo apoptotic cell death, whereas the 9L and NIH3T3 nuclei in the heterokaryons did not show the morphologic changes of apoptosis or any DNA cleavage on gels, and remained viable and mitotic. Cycloheximide prevented the induction of apoptosis in thymocyte nuclei in the heterokaryons. An excess of up to seven thymocyte nuclei undergoing programmed cell death in a heterokaryon did not detectably damage the 9L nucleus, and an excess of six 9L nuclei did not protect the thymocyte nucleus from apoptosis. The proposed model stating that programmed cell death results from de novo synthesis of death-causing gene products is difficult to reconcile with these findings. A cell-type-specific activity, present in thymocyte nuclei before induction of apoptosis with corticosteroids and unable to diffuse between nuclei, appears to be responsible for DNA fragmentation. These results also show that nuclear disintegration is the trigger of thymocyte death and not a consequence of cell death due to another mechanism.
DOI: 10.4049/jimmunol.141.8.2629
发表时间: 1988-10
影响因子: 4.4
作者:
S. Laster;J. G. Wood;L. Gooding
通讯作者: S. Laster;J. G. Wood;L. Gooding
DOI: 10.1073/pnas.87.20.8175
发表时间: 1990
影响因子: 11.1
作者:
Valtersson,C;Dutton,AH;Singer,SJ
通讯作者: Singer,SJ