Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and its inhibition by Bcl-2
Activation of Bak in ultrasound-induced, JNK- and p38-independent apoptosis and its inhibition by Bcl-2
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DOI：
10.1016/j.bbrc.2006.12.055
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发表时间：
2007-02-09
影响因子：
3.1
通讯作者：
Hynynen, Kullervo
中科院分区：
文献类型：
--
作者：
Kinoshita, Manabu;Eguchi, Yutaka;Hynynen, Kullervo
超声诱导细胞凋亡的分子机制仍知之甚少。我们已经证明，在 Jurkat 细胞中，抗凋亡蛋白 Bcl-2 的过度表达可以抑制超声诱导的细胞凋亡，但不能抑制坏死。抑制半胱天冬酶活性也可以保护细胞免于凋亡，但不能防止细胞坏死，这表明超声波诱导的细胞凋亡和坏死涉及不同的机制。 Bak 是 Bcl-2 家族蛋白的促凋亡成员，可被超声波激活，并且其激活完全被 Bcl-2 过表达所抑制，但不会被 caspase 抑制所抑制。抗氧化剂N-乙酰半胱氨酸不能保护细胞免受超声诱导的细胞凋亡或坏死，对自由基氧（ROS）介导的细胞应激反应中关键因子c-Jun N末端激酶或p38的抑制也不能保护细胞，这表明ROS在超声诱导的细胞凋亡中不起关键作用。我们的结果证实，超声波通过涉及 Bak、Bcl-2 和半胱天冬酶（但不涉及 ROS）的途径诱导细胞凋亡。 (c) 2006 Elsevier Inc. 保留所有权利。
The molecular mechanisms underlying ultrasound-induced apoptosis remain poorly understood. We have demonstrated that in Jurkat cells, the over-expression of the anti-apoptotic protein Bcl-2 inhibited ultrasound-induced apoptosis, but not necrosis. Inhibition of caspase activity also protected the cells from apoptosis, but not from necrosis, showing the involvement of different mechanisms in ultrasound-induced apoptosis and necrosis. Bak, a pro-apoptotic member of the Bcl-2 family proteins, was activated by ultrasound and its activation was completely inhibited by Bcl-2 over-expression, but not by caspase inhibition. Antioxidaut N-acetyl cysteine did not protect the cells from ultrasound-induced apoptosis or necrosis, nor did the inhibition of either c-Jun N-terminal kinase or p38, key factors in the radical oxygen species (ROS)-mediated cell stress response, suggesting that ROS do not play a crucial role in ultrasound-induced apoptosis. Our results confirm that ultrasound induces apoptosis via a pathway that involves Bak, Bcl-2, and caspases, but not ROS. (c) 2006 Elsevier Inc. All rights reserved.