Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo.
Sodium selenite alters microtubule assembly and induces apoptosis in vitro and in vivo.
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亚硒酸钠改变微管组装并诱导体外和体内细胞凋亡
DOI：
10.1186/1756-8722-6-7
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发表时间：
2013-01-17
影响因子：
28.5
通讯作者：
Xu C
中科院分区：
文献类型：
--
作者：
Shi K;Jiang Q;Li Z;Shan L;Li F;An J;Yang Y;Xu C
背景研究表明亚硒酸盐通过多种机制诱导肿瘤细胞凋亡，但亚硒酸盐对白血病细胞微管结构的影响尚未见报道。流式细胞仪检测亚硒酸钠对细胞周期分布和凋亡诱导的影响。Western blotting检测细胞周期蛋白B1、Mcl-1、AIF、细胞色素C、可溶性和不溶性微管蛋白的含量。用间接免疫荧光显微镜观察微管。CDK 1和Mcl-1之间的相互作用用免疫沉淀法评估。通过SiRNA干扰降低Mcl-1和细胞周期蛋白B1的表达。采用免疫组化和Western blotting方法检测动物模型中Mcl-1和cyclin B1的变化，原位TUNEL法检测凋亡率。此外，我们还发现HL 60细胞中微管的组装发生了改变，这些细胞被阻滞在G2/M期，Cyclin B1表达上调，并与CDK 1相互作用，导致抗凋亡蛋白Mcl-1表达下调。最后，在体内实验中证实了在体外微管的破坏作用和改变Cyclin B1和Mcl-1的水平由Seleite. Conclusions总的来说，从我们的研究结果表明，微管在白血病HL 60细胞中的硒的新目标。
BackgroundPrevious studies demonstrated that selenite induced cancer-cell apoptosis through multiple mechanisms; however, effects of selenite on microtubules in leukemic cells have not been demonstrated.MethodsThe toxic effect of selenite on leukemic HL60 cells was performed with cell counting kit 8. Selenite effects on cell cycle distribution and apoptosis induction were determined by flow cytometry. The contents of cyclin B1, Mcl-1, AIF, cytochrome C, insoluble and soluble tubulins were detected with western blotting. Microtubules were visualized with indirect immunofluorescence microscopy. The interaction between CDK1 and Mcl-1 was assessed with immunoprecipitation. Decreasing Mcl-1 and cyclin B1 expression were carried out through siRNA interference. The alterations of Mcl-1 and cyclin B1 in animal model were detected with either immunohistochemical staining or western blotting.In situdetection of apoptotic ratio was performed with TUNEL assay.ResultsOur current results showed that selenite inhibited the growth of HL60 cells and induced mitochondrial-related apoptosis. Furthermore, we found that microtubule assembly in HL60 cells was altered, those cells were arrested at G2/M phase, and Cyclin B1 was up-regulated and interacted with CDK1, which led to down-regulation of the anti-apoptotic protein Mcl-1. Finally,in vivoexperiments confirmed thein vitromicrotubule disruption effect and alterations in Cyclin B1 and Mcl-1 levels by selenite.ConclusionsTaken together, the results from our study indicate that microtubules are novel targets of selenite in leukemic HL60 cells.
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DOI：
10.1083/jcb.128.1.139
发表时间：
1995-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Tanaka E;Ho T;Kirschner MW
通讯作者：
Kirschner MW
影响因子：
3.8
作者：
Ren, Yun;Huang, Fang;Xu, Caimin
通讯作者：
Xu, Caimin
热休克蛋白90介导的核因子-κB的失活通过BECN1转录抑制在硒石诱导的NB4细胞中自噬从凋亡进行自噬。
影响因子：
3.3
作者：
Jiang Q;Wang Y;Li T;Shi K;Li Z;Ma Y;Li F;Luo H;Yang Y;Xu C
通讯作者：
Xu C
在亚硒酸盐诱导的 NB4 细胞凋亡中，ROS 通过 ERK2 易位和 p53 激活导致 MnSOD 上调
影响因子：
3.5
作者：
Li, Zhushi;Shi, Kejian;Xu, Caimin
通讯作者：
Xu, Caimin
影响因子：
4.8
作者：
Mi, Lixin;Xiao, Zhen;Chung, Fung-Lung
通讯作者：
Chung, Fung-Lung