Radiation-induced H2AX phosphorylation and neural precursor apoptosis in the developing brain of mice
Radiation-induced H2AX phosphorylation and neural precursor apoptosis in the developing brain of mice
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DOI：
10.1667/rr3496.1
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发表时间：
2006-02-01
影响因子：
3.4
通讯作者：
Boussin, FD
中科院分区：
文献类型：
--
作者：
Nowak, E;Etienne, O;Boussin, FD
我们发现，用2戈伊的γ射线照射发育中的小鼠脑，在24小时内诱导了大量的神经前体细胞凋亡，但没有神经元凋亡。组蛋白H2 AX的连续磷酸化和去磷酸化与DNA断裂和修复有关。在神经前体细胞和神经元中，在辐射后1小时发现了类似数量的磷酸化H2 AX（γ-H2 AX）的核灶，这表明辐射敏感性的差异与辐射诱导的DNA双链断裂的数量变化无关。存活的神经前体细胞如神经元在照射后24小时内完全丧失γ-H2 AX，但它们具有较慢的γ-H2 AX病灶丧失动力学。这表明DNA修复机制在这些神经前体中处理损伤的速度更慢，这与它们更高的辐射敏感性有关。我们还发现了一个明亮的和弥漫性的γ-H2 AX染色的细胞核的细胞凋亡的早期阶段，而细胞凋亡的后期阶段是未染色的。这可能与细胞凋亡过程中DNA片段化过程中H2 AX的磷酸化和随后的降解有关。因此，γ-H2 AX-亮核的检测可能是在细胞凋亡的早期阶段的神经细胞的有用标记。(c)2006年，辐射研究协会。
We showed that gamma irradiation of the developing mouse brain with 2 Gy induced a massive apoptosis of neural precursors but not of neurons within 24 h. Successive phosphorylation and dephosphorylation of histone H2AX have been linked to DNA breaks and repair. Similar numbers of nuclear foci of phosphorylated H2AX (gamma-H2AX) were found 1 h postirradiation in neural precursors and in neurons, suggesting that differences in radiosensitivity were not related to variations in the numbers, of DNA double-strand breaks induced by radiation. Surviving neural precursors like neurons totally lost gamma-H2AX within 24 h after irradiation, but they had a slower kinetics of loss of gamma-H2AX foci. This suggests that the DNA repair machinery processed damage more slowly in these neural precursors in relation to their greater radiosensitivity. We also found a bright and diffuse gamma-H2AX staining of nuclei of cells at an early stage of apoptosis, whereas cells at later stages of apoptosis were unstained. This was probably related to phosphorylation and subsequent degradation of H2AX in the course of DNA fragmentation during apoptosis. Detection of gamma-H2AX-bright nuclei may thus be a useful marker of neural cells at an early stage of apoptosis. (c) 2006 by Radiation Research Society.