Caspase-3-like activity determines the type of cell death following ionising radiation in MOLT-4 human leukaemia cells
Caspase-3-like activity determines the type of cell death following ionising radiation in MOLT-4 human leukaemia cells
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DOI：
10.1054/bjoc.2000.1322
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发表时间：
2000-09-01
影响因子：
8.8
通讯作者：
Bischoff, P
中科院分区：
文献类型：
--
作者：
Coelho, D;Holl, V;Bischoff, P
半胱氨酸蛋白酶（Caspase）家族在细胞凋亡过程中起重要作用。近年来，有报道称Caspase的广谱抑制剂Z-VAD-favorite可诱导地塞米松处理的B淋巴细胞和胸腺细胞由凋亡向坏死转变。由于这种细胞死亡转换可以增加放射治疗的效率，并且为了鉴定参与这种细胞死亡转换的半胱天冬酶，我们研究了半胱天冬酶-3相关蛋白酶抑制在辐照的MOLT-4细胞中的作用。用Ac-DEVD-CHO（半胱天冬酶-3样活性的抑制剂）预处理细胞，并以1至4戈伊的剂量进行X射线照射。我们的研究结果表明，caspase-3样活性的抑制完全防止了经典的细胞凋亡的标志，如核小体间DNA片段化或亚二倍体颗粒的形成和部分磷脂酰丝氨酸的外化的外观。然而，这并不伴随着细胞存活的任何持续增加。相反，用这种抑制剂处理的辐照细胞表现出坏死细胞死亡的特征。因此，功能性caspase-3-亚家族不仅在凋亡过程的执行中作为关键蛋白酶出现，而且它们的活性也可能影响电离辐射暴露后细胞死亡的类型。(C)2000年癌症研究运动。
Caspases, a family of cysteine proteases, play a central role in the pathways leading to apoptosis, Recently, it has been reported that a broad spectrum inhibitor of caspases, the tripeptide Z-VAD-fmk, induced a switch from apoptosis to necrosis in dexamethasone-treated B lymphocytes and thymocytes. As such a cell death conversion could increase the efficiency of radiation therapy and in order to identify the caspases involved in this cell death transition, we investigated the effects of caspase-3-related proteases inhibition in irradiated MOLT-4 cells. Cells were pretreated with Ac-DEVD-CHO, an inhibitor of caspase-3-like activity, and submitted to X-rays at doses ranging from 1 to 4 Gy. Our results show that the inhibition of caspase-3-like activity prevents completely the appearance of the classical hallmarks of apoptosis such as internucleosomal DNA fragmentation or hypodiploid particles formation and partially the externalization of phosphatidylserine. However, this was not accompanied by any persistent increase in cell survival. Instead, irradiated cells treated by this inhibitor exhibited characteristics of a necrotic cell death. Therefore, functional caspase-3-subfamily not only appears as key proteases in the execution of the apoptotic process, but their activity may also influence the type of cell death following an exposure to ionizing radiation. (C) 2000 Cancer Research Campaign.