TP53 and TP53-related genes associated with protection from apoptosis in the radioadaptive response

TP53 and TP53-related genes associated with protection from apoptosis in the radioadaptive response
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DOI:
10.1667/rr0623.1
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发表时间:
2007-01-01
期刊:
影响因子:
3.4
通讯作者:
Norimura, Toshiyuki
Norimura, Toshiyuki
中科院分区:
医学3区
文献类型:
--
作者:
Okazaki, Ryuji;Ootsuyama, Akira;Norimura, Toshiyuki

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我们研究了在高剂量辐射之前给予引发低剂量辐射对小鼠脾细胞凋亡水平和TP 53及其相关基因表达的影响。与单独接受2戈伊照射的TP 53(+/+)小鼠相比,在高剂量照射前2 ~ 168 h接受预激照射的TP 53(+/+)小鼠的凋亡细胞百分比显著降低。相反,TP 53(+/-)小鼠表现出降低的细胞凋亡水平时,只有在高剂量照射前进行了2或4小时的启动。在TP 53(+/+)小鼠中,致敏小鼠的TP 53表达高于暴露于2戈伊的小鼠。磷酸化TP 53(ser 15/18)表达在暴露于2戈伊的小鼠中最高,在致敏小鼠中居中。与暴露于2戈伊的小鼠相比,p21(CDKN 1A)的表达在致敏小鼠中更高。在接受2戈伊的所有小鼠中,MDM 2表达保持在高水平。仅在暴露于2戈伊的小鼠中观察到磷酸-ATM表达升高。我们的结论是,TP 53在辐射适应性反应中起着至关重要的作用,TP 53和TP 53相关基因可能通过激活细胞内修复系统来保护细胞免于凋亡。(c)2007年,辐射研究协会。
We investigated the effect of administering priming low-dose radiation prior to high-dose radiation on the level of apoptosis and on the expression of TP53 and TP53-related genes in mouse splenocytes. The percentage of apoptotic cells was significantly lower in TP53(+/+) mice receiving priming radiation 2 to 168 h before the high-dose irradiation, compared to TP53(+/+) mice exposed to 2 Gy alone. In contrast, TP53(+/-) mice exhibited a reduced level of apoptosis only when priming was performed for 2 or 4 h prior to the high-dose irradiation. In TP53(+/+) mice, primed mice had higher TP53 expression than mice exposed to 2 Gy. Phospho-TP53 (ser15/18) expression was the highest in mice exposed to 2 Gy and intermediate in primed mice. Expression of p21 (CDKN1A) was higher in primed mice compared with mice exposed to 2 Gy. MDM2 expression remained at a high level in all mice receiving 2 Gy. Elevated phospho-ATM expression was observed only in mice exposed to 2 Gy. We conclude that TP53 plays a critical role in the radioadaptive response and that TP53 and TP53-related genes might protect cells from apoptosis through activation of the intracellular repair system. (c) 2007 by Radiation Research Society.