Post-irradiation hypoxic incubation of X-irradiated MOLT-4 cells reduces apoptotic cell death by changing the intracellular redox state and modulating SAPK/JNK pathways
Post-irradiation hypoxic incubation of X-irradiated MOLT-4 cells reduces apoptotic cell death by changing the intracellular redox state and modulating SAPK/JNK pathways
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DOI：
10.1007/s10495-005-1888-x
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发表时间：
2005-05-01
期刊：
影响因子：
7.2
通讯作者：
Kuwabara, M
中科院分区：
文献类型：
--
作者：
Hamasu, T;Inanami, O;Kuwabara, M
为了阐明缺氧对X射线诱导的细胞凋亡的放射生物学效应，在四组条件下处理MOLT-4细胞：（1）X射线照射和常氧孵育，（2）X射线低氧照射和随后常氧孵育，（3）X射线常氧照射和随后低氧孵育，和（4）X射线照射和低氧孵育，荧光显微镜观察细胞凋亡的诱导作用。在条件1和2下处理的细胞中观察到约28-33%的细胞凋亡，但在条件3和4下处理的细胞中该值显著降低至约18-20%，表明辐射后低氧孵育而不是低氧辐射主要引起细胞凋亡的减少。凋亡信号相关分子SAPK/JNK、Fas和caspase-3的活化和表达也被低氧孵育抑制。缺氧孵育的影响被取消时，细胞在条件3和4下处理与氧模拟缺氧细胞放射增敏剂，而另外的N-乙酰-L-半胱氨酸再次减少诱导细胞凋亡。从这些结果可以得出结论，缺氧通过改变细胞内的氧化还原状态，然后通过调节X射线照射的MOLT-4细胞的凋亡信号，减少诱导凋亡。
To elucidate radiobiological effects of hypoxia on X-ray-induced apoptosis, MOLT-4 cells were treated under four set of conditions: (1) both X irradiation and incubation under normoxia, (2) X irradiation under hypoxia and subsequent incubation under normoxia, (3) X irradiation under normoxia and subsequent incubation under hypoxia, and (4) both X irradiation and incubation under hypoxia, and the induction of apoptosis was examined by fluorescence microscopy. About 28-33% apoptosis was observed in cells treated under conditions 1 and 2, but this value was significantly reduced to around 18-20% in cells treated under conditions 3 and 4, suggesting that post-irradiation hypoxic incubation rather than hypoxic irradiation mainly caused the reduction of apoptosis. The activation and expression of apoptosis signal-related molecules SAPK/JNK, Fas and caspase-3 were also suppressed by hypoxic incubation. Effects of hypoxic incubation were canceled when cells were treated under conditions 3 and 4 with an oxygen-mimicking hypoxic cell radiosensitizer, whereas the addition of N-acetyl-L-cysteine again reduced the induction of apoptosis. From these results it was concluded that hypoxia reduced the induction of apoptosis by changing the intracellular redox state, followed by the regulation of apoptotic signals in X-irradiated MOLT-4 cells.