Chromatin condensation during apoptosis requires ATP
Chromatin condensation during apoptosis requires ATP
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DOI：
10.1042/bj3180749
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发表时间：
1996-09-15
影响因子：
4.1
通讯作者：
Chow, SC
中科院分区：
文献类型：
--
作者：
Kass, GEN;Eriksson, JE;Chow, SC
细胞凋亡过程中染色质形态学改变的过程目前尚不清楚。我们最近的研究表明，染色质断裂和凋亡中典型的核形态变化在体外系统中重现，该系统由分离的大鼠胸腺细胞核组成，在Fas/ apo -1刺激的JURKAT细胞的裂解物存在下孵育[Chow， Weis, Kass, Holmstrom， Eriksson和Orrenius (1995) FEBS Lett. 364, 134-138]。利用这种体外系统，我们现在报道ATP的存在是染色质凝聚、向核周围运动和凋亡小体形成所必需的。与此形成鲜明对比的是，Fas/ apo -1激活的JURKAT细胞裂解物诱导的染色质裂解成高分子量和低核小体长度的DNA片段不需要ATP的存在。ATP对这些形态变化的诱导作用是类似物5′-[β， γ -亚甲基]三磷酸腺苷和5′-[α， β -亚甲基]三磷酸腺苷、AMP、cAMP和UTP所不能替代的。然而，腺苷5'[γ -硫]三磷酸，以及GTP和ADP在较小程度上可以部分取代ATP诱导核凋亡的形态学改变。结果表明，在细胞凋亡过程中，ATP对细胞核的形态变化是必需的，而对DNA的断裂则不是必需的。
The processes leading to morphological changes of the chromatin in cells that undergo apoptosis are presently unclear. We have recently shown that chromatin fragmentation and the nuclear morphological changes typically seen in apoptosis were reproduced in an in vitro system comprised of isolated rat thymocyte nuclei incubated in the presence of a lysate from Fas/APO-1-stimulated JURKAT cells [Chow, Weis, Kass, Holmstrom, Eriksson and Orrenius (1995) FEBS Lett. 364, 134-138]. Using this in vitro system, we now report that the presence of ATP is necessary for chromatin condensation, its movement to the nuclear periphery and apoptotic body formation. In clear contrast, chromatin cleavage into high-molecular-mass and oligo-nucleosomal-length DNA fragments induced by lysates derived from Fas/APO-1-activated JURKAT cells did not require the presence of ATP. The induction of these morphological changes by ATP could not be substituted by the analogues, adenosine 5'-[beta,gamma-methylene]triphosphate and adenosine 5'-[alpha,beta-methylene]triphosphate, AMP, cAMP and UTP. However, adenosine 5'[gamma-thio]triphosphate, and to a lesser degree GTP and ADP, could partially replace ATP in inducing nuclear apoptotic morphological changes. It is concluded that ATP is essential for the morphological changes occurring in nuclei during apoptosis, but not for DNA fragmentation.