Colistin-induced apoptosis in PC12 cells: Involvement of the mitochondrial apoptotic and death receptor pathways
Colistin-induced apoptosis in PC12 cells: Involvement of the mitochondrial apoptotic and death receptor pathways
复制标题
粘菌素诱导的 PC12 细胞凋亡：线粒体凋亡和死亡受体途径的参与
DOI：
10.3892/ijmm.2014.1684
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发表时间：
2014-05-01
影响因子：
5.4
通讯作者：
Wang, Hongjun
中科院分区：
文献类型：
--
作者：
Jiang, Hong;Li, Jichang;Wang, Hongjun
粘菌素是一种环阳离子多肽抗生素，用于治疗感染，可能导致神经毒性。然而，粘菌素是否能诱导PC12细胞凋亡以及其凋亡的确切机制尚不清楚。本研究的目的是通过western blotting检测硫酸粘菌素处理PC12细胞的活性氧（ROS）水平和DNA损伤，以及p53、细胞色素c、Bax、Bcl-2、Fas、Fas- l和caspase家族等凋亡因子。结果表明，硫酸粘菌素显著提高了ROS水平。ROS水平的增加诱导细胞色素c的释放和DNA损伤。DNA损伤可激活p53，导致Bax上调，Bcl-2下调。Bax/Bcl-2的失衡促进了细胞色素c的额外释放。细胞色素c的释放有助于caspase-9的激活以及随后的caspase-3的激活。Fas和Fas- l的增加诱导caspase-8的活化导致caspase- 3的活化，后者诱导细胞凋亡。因此，这些结果表明，粘菌素诱导PC12细胞凋亡的凋亡途径涉及线粒体和死亡受体两种途径。
Colistin, a cyclic cationic polypeptide antibiotic that is used to treat infections, may cause neurotoxicity. However, whether colistin can induce apoptosis and the precise mechanism of apoptosis involved in PC12 cells remains to be determined. The aim of the present study was to determine reactive oxygen species (ROS) level and DNA damage, as well as apoptotic factors such as p53, cytochrome c, Bax, Bcl-2, Fas, Fas-L and caspase family via western blotting in PC12 cells treated with colistin sulfate. The results showed that colistin sulfate increased ROS levels significantly. An increase of ROS levels induces the release of cytochrome c and DNA damage. DNA damage can activate p53, which leads to the upregulation of Bax and downregulation of Bcl-2. The imbalance of Bax/Bcl-2 promotes additional release of cytochrome c. The release of cytochrome c contributes to the activation of caspase-9 and the subsequent activation of caspase-3. An increase of Fas and Fas-L induced the activation of caspase-8 leading to the activation of caspases-3, the latter induces apoptosis. Therefore, these results demonstrate that the apoptotic pathway of colistin-induced apoptosis in PC12 cells is involved in both the mitochondrial and death receptor pathway.