A comprehensive study of p53 transcriptional activity in thymus and spleen of γ irradiated mouse:: High sensitivity of genes involved in the two main apoptotic pathways
A comprehensive study of p53 transcriptional activity in thymus and spleen of γ irradiated mouse:: High sensitivity of genes involved in the two main apoptotic pathways
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DOI：
10.1080/09553000600949624
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发表时间：
2006-11-01
影响因子：
2.6
通讯作者：
May, Evelyne
中科院分区：
文献类型：
--
作者：
Alvarez, Sandra;Drane, Pascal;May, Evelyne
目的：γ辐照导致p53肿瘤抑制基因的激活和p53依赖性刺激大量细胞基因，包括参与内源性和外源性途径的促凋亡基因。大多数已发表的体内数据涉及高（致死）辐照剂量。本研究的目的是分析p53依赖性对更相关的低辐照剂量的反应。材料和方法：小鼠全身暴露于5 ~ 0.05 Gy剂量递减的辐照下。通过实时逆转录酶聚合酶链反应测定从胸腺和脾脏提取的RNA的基因表达。通过膜联蛋白V阳性或亚g1细胞的百分比来评估细胞凋亡。结果：0.1 Gy的照射剂量已经可以显著刺激Puma （p53上调的凋亡调节剂），以及0.2 Gy的Bax （bcl -2相关X蛋白）和Killer/DR5（死亡受体5）。两种凋亡通路相关基因的表达在照射后1小时即被诱导，并在照射后3小时达到峰值，诱导水平取决于基因和器官。结论：我们的研究结果揭示了p53依赖性转录激活参与两种主要凋亡通路的基因的高体内敏感性，它们的刺激在诱导凋亡之前。
Purpose: gamma-irradiation leads to activation of p53 tumour suppressor gene and to p53-dependant stimulation of a large panel of cellular genes including proapoptotic genes involved in intrinsic and extrinsic pathways. Most in vivo published data referred to high ( lethal) irradiation doses. The present study was performed to analyse the p53-dependent response to more relevant low irradiation doses.Materials and methods: Mice were whole body exposed to irradiation doses decreasing from 5-0.05 Gy. Gene expression was estimated by real time reverse transcriptase polymerase chain reaction measurements on RNA extracted from thymus and spleen. Apoptosis was evaluated by the percentage of either annexin V positive or sub-G1 cells.Results: A 0.1 Gy irradiation dose already gives a significant stimulation of Puma ( p53 up-regulated modulator of apoptosis), and 0.2 Gy of Bax (Bcl-2-associated X protein) and Killer/DR5 (Death Receptor 5). The expression of genes involved in the two apoptotic pathways was induced as soon as 1 h post-irradiation and reached a maximum at 3 h, the induction level depending on both the gene and the organ. A significant increase in the number of apoptotic cells is already detectable at 0.5 Gy with a maximum of induction at 6 h.Conclusions: Our results reveal the high in vivo sensitivity of p53-dependent transcriptional activation of genes involved in the two main apoptotic pathways, their stimulation preceding the induction of apoptosis.