The involvement of reactive oxygen species (ROS) and p38mitogen-activated protein (MAP) kinase in TRAIL/Apo2L-induced apoptosis
The involvement of reactive oxygen species (ROS) and p38mitogen-activated protein (MAP) kinase in TRAIL/Apo2L-induced apoptosis
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DOI：
10.1016/s0014-5793(02)02225-1
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发表时间：
2002-02-13
期刊：
影响因子：
3.5
通讯作者：
Kim, SS
中科院分区：
文献类型：
--
作者：
Lee, MW;Park, SC;Kim, SS
为探讨肿瘤坏死因子相关凋亡诱导配体（TRAIL/Apo 2L）诱导的细胞凋亡信号通路，我们研究了活性氧（ROS）、p38丝裂原活化蛋白（MAP）激酶和半胱天冬酶在人腺癌HeLa细胞中的作用。在这里，我们表明，在TRAIL/Apo 2L曝光有明显的ROS积累和激活的p38 MAP激酶，激活半胱天冬酶和凋亡。用抗氧化剂如谷胱甘肽或雌激素预处理通过减少ROS的产生和减少p38 MAP激酶和半胱天冬酶的激活来减弱TRAIL/Apo 2L诱导的细胞凋亡。p38 MAP激酶抑制剂SB 203580通过阻断caspase活化来防止细胞凋亡，尽管ROS的产生没有减弱。此外，泛半胱天冬酶抑制剂Z-Val-Ala-DL-Asp-fluoromethyl ketone完全阻止细胞凋亡，而ROS积累和p38 MAP激酶激活均不受影响。因此，我们的研究结果表明，TRAIL/Apo 2L诱导的细胞凋亡是由ROS激活的p38 MAP激酶介导的，随后在HeLa细胞中激活caspase。(C)2002年由Elsevier Science B. V.代表欧洲生物化学学会联合会出版。
To determine the apoptotic signaling pathway which tumor necrosis factor-related apoptosis-inducing ligand (TRAIL/Apo2L) induced, we investigated the contribution of reactive oxygen species (ROS), p38 mitogen-activated protein (MAP) kinase and caspases in human adenocarcinoma HeLa cells. Here we show that upon TRAIL/Apo2L exposure there was pronounced ROS accumulation and activation of p38 MAP kinase, and that activation of caspases and apoptosis followed. Pretreatment with antioxidants such as glutathione or estrogen attenuated TRAIL/Apo2L-induced apoptosis through a reduction of ROS generation and diminished p38 MAP kinase and caspase activation. The p38 MAP kinase inhibitor SB203580 prevented apoptosis through a blockage of caspase activation, although ROS generation was not attenuated. Furthermore, the pan-caspase inhibitor Z-Val-Ala-DL-Asp-fluoromethyl ketone fully prevented apoptosis, while neither ROS accumulation nor p38 MAP kinase activation were affected. Therefore, our results suggest that TRAIL/Apo2L-induced apoptosis is mediated by ROS-activated p38 MAP kinase followed by caspase activation in HeLa cells. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.