Akt1 suppresses radiation-induced germ cell apoptosis in vivo
Akt1 suppresses radiation-induced germ cell apoptosis in vivo
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DOI：
10.1210/en.2006-0174
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发表时间：
2006-09-01
期刊：
影响因子：
4.8
通讯作者：
Hixon, Mary
中科院分区：
文献类型：
--
作者：
Rasoulpour, Teresa;DiPalma, Kathryn;Hixon, Mary
辐射暴露是一种充分表征的生殖细胞损伤模型，导致细胞周期停滞或凋亡。丝氨酸-苏氨酸激酶Akt 1与抑制由不同刺激诱导的细胞死亡有关，所述刺激包括生长因子撤除、细胞周期不一致、DNA损伤和细胞粘附丧失。然而，在睾丸中，这种促生存途径的体内相关性尚未探讨。为了评估Akt 1在体内睾丸中的保护作用，我们研究了辐射诱导的生殖细胞损伤后Akt 1缺陷小鼠的凋亡发生率。我们发现，Akt激酶活性增加，在野生型小鼠的睾丸电离辐射后，和Akt 1的损失的结果在一个早期发生的生殖细胞凋亡和增强敏感性的有丝分裂精原细胞电离辐射。在mRNA和蛋白质水平上，Akt 1不存在时，Akt 2和Akt 3的表达均未被诱导。这些数据表明，在辐射诱导的睾丸损伤后生殖细胞的存活中，Akt 1和Akt 2（在较小程度上）具有重要的存活功能。此外，结果指出Fas配体在调节这种反应中的作用。
Radiation exposure is a well-characterized germ cell injury model leading to cell cycle arrest or apoptosis. The serine-threonine kinase, Akt1, has been implicated in inhibiting cell death induced by different stimuli including growth factor withdrawal, cell cycle discordance, DNA damage, and loss of cell adhesion. However, the in vivo relevance of this prosurvival pathway has not been explored in the testis. To evaluate a protective role for Akt1 in the testis in vivo, we examined the incidence of apoptosis in Akt1-deficient mice after radiation-induced germ cell injury. We found that Akt kinase activity increases in the testes of wild-type mice after ionizing radiation, and that loss of Akt1 results in an earlier onset of germ cell apoptosis and enhanced sensitivity of mitotic spermatogonia to ionizing radiation. At both the mRNA and protein level, neither Akt2 nor Akt3 expression were induced in the absence of Akt1. These data demonstrate an important survival function governed by Akt1 and, to a lesser extent, Akt2 in the survival of germ cells after radiation-induced testicular injury. In addition, the results point to a role for Fas ligand in the regulation of this response.