Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy

Involvement of MAPK activation and ROS generation in human leukemia U937 cells undergoing apoptosis in response to sonodynamic therapy
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MAPK 激活和 ROS 生成参与人白血病 U937 细胞响应声动力治疗而发生凋亡

DOI:
10.3109/09553002.2013.817700
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发表时间:
2013-06
影响因子:
2.6
通讯作者:
Quanhong Liu
Quanhong Liu
中科院分区:
医学3区
文献类型:
--
作者:
Xiaomin Su;Pan Wang;Xiaobing Wang;Ling Guo;Silu Li;Quanhong Liu

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摘要目的:目的探讨二氢卟酚e6(Ce 6)介导的声动力疗法(Ce 6-SDT)诱导人白血病细胞株U937凋亡的机制。材料与方法:采用MTT法检测细胞活力。采用流式细胞仪和荧光显微镜4′-6-Diamidino-2-Phenylindole(DAPI)染色法检测细胞凋亡。Western blotting检测caspase-3、多聚腺苷二磷酸核糖聚合酶(PARP)和丝裂原活化蛋白激酶(MAPK)的表达。结果:SDT处理后出现了几种明显的声化学效应。MAPK信号参与了SDT诱导的U937细胞损伤,抑制p38 MAPK和JNK对SDT诱导的U937细胞死亡有明显的抑制作用,而抑制细胞外信号调节激酶(ERK 1/2)则增强了SDT诱导的U937细胞死亡。SDT可显著增加细胞内活性氧(ROS)的含量,NAC可部分抑制SDT诱导的细胞活力下降、DNA断裂、线粒体膜电位(MMP)降低和caspase-3激活,但对MAPK的激活无明显影响。结论:Ce 6-SDT可明显促进U937细胞凋亡。p38 MAPK、JNK和ERK在此过程中均有不同程度的激活。对诱导的细胞凋亡的一种可能的解释可能是Ce 6-SDT中增加的ROS产生。
Abstract Purpose: To elucidate the underlying events in Chlorin e6 (Ce6)-mediated sonodynamic therapy (SDT) (Ce6-SDT)-induced apoptosis of human leukemia cell line U937. Materials and methods: The viability of cells was determined by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltertrazolium bromide tetrazolium (MTT) test. Apoptosis was analyzed using a flow cytometer as well as fluorescence microscopy with 4′-6-Diamidino-2-Phenylindole (DAPI) staining. Western blotting was used to analyze the expression of caspase-3, poly ADP- ribose polymerase (PARP) and mitogen-activated protein kinase (MAPK). Results: Several distinct sonochemical effects were found after SDT treatment. The participation of MAPK signals in SDT which caused U937 cell damage was specifically examined and the inhibition of p38 MAPK and Jun-N-terminal kinase (JNK) both apparently exerted a negative effect on SDT-induced cell death, while extracellular signal-regulating kinase (ERK1/2) inhibition enhanced SDT-induced cell death. The intracellular reactive oxygen species (ROS) was significantly enhanced by SDT, and pre-treatment with ROS scavenger N-acetylcysteine (NAC) partially alleviated SDT-induced cell viability loss, DNA fragmentation, mitochondria membrane potential (MMP) dissipation, caspase-3 activation, but interestingly MAPK activation was not affected much by NAC. Conclusions: In the present paper, cell apoptosis of U937 cells was markedly enhanced after Ce6-SDT. Meanwhile, p38 MAPK, JNK and ERK were all differently activated in this process. One possible explanation for the induced cell apoptosis could be the increased ROS generation in Ce6-SDT.
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发表时间: 2006-03-01
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