Enokido Y, Araki T, Aizawa S, Hatanaka H
Institute for Protein Research, Osaka University, Japan.
Neurosci Lett. 1996 Jan 12;203(1):1-4. doi: 10.1016/0304-3940(95)12247-8.
The tumor suppressor p53 gene plays a key role in controlling the cell cycle checkpoint and in apoptosis following the exposure of normal cells to DNA damage. To investigate the role of p53 in cytosine arabinoside (Ara C)-induced cell death of CNS neurons, we examined the effect of Ara C on the survival of cultured cerebellar granule neurons from normal wild-type and p53 null mutant mice. When the neurons from wild-type mice were cultured with Ara C, they gradually died after 24 h in culture. In contrast, the neurons from p53 null mutant mice showed a resistance to the Ara C neurotoxicity. These results indicate that p53 involves Ara C-induced apoptosis in cultured cerebellar granule neurons, in which DNA damage may initiate the apoptotic death program of the neurons.
肿瘤抑制基因p53在控制细胞周期检查点以及正常细胞暴露于DNA损伤后诱导细胞凋亡过程中发挥关键作用。为了研究p53在阿糖胞苷(Ara C)诱导的中枢神经系统神经元细胞死亡中的作用,我们检测了Ara C对来自正常野生型和p53基因敲除突变型小鼠的培养小脑颗粒神经元存活的影响。当野生型小鼠的神经元与Ara C一起培养时,它们在培养24小时后逐渐死亡。相比之下,p53基因敲除突变型小鼠的神经元对Ara C神经毒性具有抗性。这些结果表明,p53参与了Ara C诱导的培养小脑颗粒神经元凋亡,其中DNA损伤可能启动神经元的凋亡死亡程序。