Mechanism of apoptosis induced by copper in PC12 cells
Mechanism of apoptosis induced by copper in PC12 cells
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DOI：
10.1016/j.fct.2008.02.014
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发表时间：
2008-06-01
影响因子：
4.3
通讯作者：
Kurasaki, Masaaki
中科院分区：
文献类型：
--
作者：
Kawakami, Masaki;Inagawa, Rieko;Kurasaki, Masaaki
铜是一种必需的微量元素，可诱导哺乳动物细胞凋亡。然而，铜诱导细胞凋亡的确切机制仍不清楚。本研究通过Western印迹和RT-PCR方法检测了铜诱导的PC12细胞中Bax、Bad、Bcl2等凋亡因子和caspase家族的表达，以探讨铜诱导PC12细胞凋亡的途径。铜处理后Bax、Bad、细胞色素c、半胱氨酸天冬氨酸蛋白酶3和9的表达增加。根据这些结果，提出了铜诱导细胞凋亡的两条途径。首先，Bax的增加导致细胞色素c从线粒体释放到细胞质中，与凋亡激活的caspase9结合，导致caspase3的激活。在另一种途径中，Bax的增加和活性氧的增加激活了线粒体AIF的释放。AIF通过不依赖于caspase的途径诱导细胞凋亡。(C)2008爱思唯尔有限公司。保留所有权利。
Copper, an essential trace element, induces apoptosis in mammalian cells. However, the precise mechanism of copper-induced apoptosis is still unclear. In this study, to determine the apoptotic pathway initiated by copper treatment, apoptotic factors such as Bax, Bad and Bcl-2, and the caspase family in PC 12 cells treated with copper were measured by Western blot and RT-PCR analyses. The expression of Bax, Bad, cytochrome c and caspases 3 and 9 were increased by copper treatment. From these results, two pathways for copper-induced apoptosis were suggested. At first, an increase of Bax induces the release of cytochrome c from the mitochondria into the cytoplasm owing to binding to apoptotic activating caspase 9 leading to the activation of caspases 3. In the other pathway an increase of Bax and reactive oxygen species activates the release of AIF from the mitochondria. The AIF induces apoptosis via a caspase-independent pathway. (C) 2008 Elsevier Ltd. All rights reserved.