Hyperthermia induces translocation of apoptosis-inducing factor (AIF) and apoptosis in human glioma cell lines
Hyperthermia induces translocation of apoptosis-inducing factor (AIF) and apoptosis in human glioma cell lines
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DOI：
10.1007/s11060-004-9168-0
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发表时间：
2004-12-01
影响因子：
3.9
通讯作者：
Matsuda, M
中科院分区：
文献类型：
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作者：
Fukami, T;Nakasu, S;Matsuda, M
在高温处理中，野生型p53在肿瘤细胞的凋亡诱导中起重要作用。在人类神经胶质瘤中，p53经常有某种形式的突变。突变型（mt）p53不能作为肿瘤抑制因子正常工作，这可能导致治疗期间的不良反应。我们使用四种p53野生型或突变型人脑胶质瘤细胞系（A172、T98 G、U251 MG和YKG-1）研究了在不同热条件（43、45和47 ℃，1 h）下凋亡诱导因子（AIF）与凋亡的关系。在高温条件下，AIF从线粒体易位到细胞核，通过激光共聚焦显微镜证实。与对照组相比，除YKG-1在47 ℃时外，所有细胞系和所有温度组中AIF阳性细胞核的百分比均显著增加。每个细胞系的核部分的免疫印迹分析显示AIF的温度依赖性增加。细胞色素c同时从线粒体释放到细胞质中。流式细胞仪分析表明，在45和47 degreesC组中，凋亡诱导以温度依赖性方式发生的频率高于对照组。这些结果表明，高温条件下可以导致AIF易位和p53突变的人胶质瘤细胞凋亡。本报告是第一次描述AIF诱导的细胞凋亡在高温。
In the hyperthermal treatment, the wild type (wt) p53 plays an important role in apoptosis induction in the tumor cells. In human gliomas, p53 frequently has some form of mutation. The mutant type (mt) p53 does not work properly as a tumor suppressor and this may result in poor responses during treatment. We investigated the relationship between apoptosis-inducing factor (AIF) and apoptosis under various thermal conditions (43, 45, and 47degreesC for 1 h) using four p53-wild or -mutant human glioma cell lines (A172, T98G, U251MG, and YKG-1). AIF translocation from the mitochondria to the nucleus under hyperthermal conditions was demonstrated by confocal laser microscopy. The percentage of AIF-positive nuclei increased significantly in comparison with the control in all cell lines and in all temperature groups except for YKG-1 at 47degreesC. Immunoblot analyses of the nuclear fraction of each cell line revealed temperature-dependent increases in AIF. A simultaneous release of cytochrome c from the mitochondria to the cytosol was noted. A flow cytometric analysis showed that apoptosis induction occurred more often in a temperature-dependent manner in the 45 and 47degreesC groups than in the control group. These findings indicate that the hyperthermal conditions can lead to AIF translocation and apoptotic cell death in the p53-mutant human glioma cells. The present report is the first description of AIF-induced apoptosis in hyperthermia.