College of Animal Husbandry and Veterinary Medicine, Liaoning Medical University, Jinzhou, Liaoning 121001, P.R. China.
College of Veterinary Medicine, Northeast Agricultural University, Harbin, Heilongjiang 150030, P.R. China.
Int J Mol Med. 2014 May;33(5):1298-304. doi: 10.3892/ijmm.2014.1684. Epub 2014 Mar 6.
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.
黏菌素是一种用于治疗感染的环状阳离子多肽抗生素，可能会引起神经毒性。然而，黏菌素是否能诱导 PC12 细胞凋亡以及涉及的凋亡的确切机制尚待确定。本研究旨在通过 Western blot 法检测硫酸黏菌素处理的 PC12 细胞中活性氧（ROS）水平和 DNA 损伤，以及 p53、细胞色素 c、Bax、Bcl-2、Fas、Fas-L 和半胱天冬酶家族等凋亡因子。结果表明，硫酸黏菌素显著增加了 ROS 水平。ROS 水平的升高会诱导细胞色素 c 的释放和 DNA 损伤。DNA 损伤可激活 p53，导致 Bax 上调和 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，进而激活 caspase-3。Fas 和 Fas-L 的增加诱导了 caspase-8 的激活，导致 caspase-3 的激活，后者诱导细胞凋亡。因此，这些结果表明，黏菌素诱导 PC12 细胞凋亡的凋亡途径涉及线粒体和死亡受体途径。
