P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death
P2Z purinoreceptor ligation induces activation of caspases with distinct roles in apoptotic and necrotic alterations of cell death
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DOI：
10.1016/s0014-5793(99)00270-7
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发表时间：
1999-03-19
期刊：
影响因子：
3.5
通讯作者：
Schulze-Osthoff, K
中科院分区：
文献类型：
--
作者：
Ferrari, D;Los, M;Schulze-Osthoff, K
骨髓细胞表达一种特殊的细胞外 ATP 表面受体，称为 P2Z/P2X(7) 嘌呤受体，它参与细胞死亡信号传导。在这里，我们研究了半胱天冬酶（半胱天冬酶）的作用，半胱天冬酶是与细胞凋亡和细胞因子分泌有关的蛋白酶家族。我们观察到细胞外 ATP 诱导多种 caspase 的激活，包括 caspase-1、-3 和 -8，以及随后 caspase 底物 PARP 和 Iamin B 的裂解。使用 caspase 抑制剂，发现 caspase 特异性参与 ATP 诱导的细胞凋亡损伤，如染色质浓缩和 DNA 片段化，相比之下，caspase 的抑制仅轻微影响 无论核损伤是否被阻断，坏死性改变和细胞死亡都会正常进行。因此，我们的结果表明，P2Z 受体激活半胱天冬酶是 ATP 诱导的细胞死亡发生凋亡而非坏死改变所必需的。 (C) 1999 年欧洲生化学会联合会。
Myeloic cells express a peculiar surface receptor for extracellular ATP, called the P2Z/P2X(7) purinoreceptor, which is involved in cell death signalling. Here, we investigated the role of caspases, a family of proteases implicated in apoptosis and the cytokine secretion. We observed that extracellular ATP induced the activation of multiple caspases including caspase-1, -3 and -8, and subsequent cleavage of the caspase substrates PARP and Iamin B. Using caspase inhibitors, it was found that caspases were specifically involved in ATP-induced apoptotic damage such as chromatin condensation and DNA fragmentation, In contrast, inhibition of caspases only marginally affected necrotic alterations and cell death proceeded normally whether or not nuclear damage was blocked. Our results therefore suggest that the activation of caspases by the P2Z receptor is required for apoptotic but not necrotic alterations of ATP-induced cell death. (C) 1999 Federation of European Biochemical Societies.