Uberti D, Meli E, Memo M
Department of Biomedical Sciences and Biotechnologies, University of Brescia Medical School, Brescia, Italy.
Amino Acids. 2002;23(1-3):27-30. doi: 10.1007/s00726-001-0105-7.
Previous work from our laboratory has suggested the functional contribution of p53 to the cascade of events triggered by excitatory amino acids and leading to cell death in primary neurons. Here we show that this paradigm can be extended to cortical neurons treated with NMDA. We found that exposure of the cells to either 300 microM or 2 mM NMDA induced an enhancement of p53 protein levels which was already significant at 60 min after the lesion, while very low staining of the protein was observed in untreated cells. The effect was time- and concentration-dependent, reaching the maximal induction at 3 h. NMDA treatment also resulted in an increase of gadd45 protein levels which was evident in both treatment at 3 h, the time when p53 was maximally induced. Our data give further evidence suggesting that a repertoire of events typical of proliferating cells is activated in degenerating neurons.
我们实验室之前的研究表明，p53在由兴奋性氨基酸触发并导致原代神经元细胞死亡的一系列事件中发挥了功能性作用。在此我们表明，这一模式可扩展至用N-甲基-D-天冬氨酸（NMDA）处理的皮质神经元。我们发现，将细胞暴露于300微摩尔或2毫摩尔的NMDA中会导致p53蛋白水平升高，损伤后60分钟时该升高已很显著，而未处理的细胞中该蛋白染色非常低。这种效应具有时间和浓度依赖性，在3小时时达到最大诱导程度。NMDA处理还导致生长停滞和DNA损伤诱导蛋白45（gadd45）水平升高，在3小时的两种处理中均很明显，而这正是p53被最大程度诱导的时间。我们的数据进一步证明，在退化的神经元中，典型的增殖细胞事件谱被激活。
