J Mol Neurosci. 2013 Nov;51(3):695-702. doi: 10.1007/s12031-013-0050-4.
Traumatic brain injury (TBI) initiates a series of complicated pathological events that could eventually lead to neuronal apoptosis. Recent studies indicated that p53 played a crucial role in neuronal apoptosis and regeneration following TBI. However, the detailed mechanism of p53-induced neuronal apoptosis in TBI remains largely elusive. In this study, we identified that p53-induced death domain protein (PIDD), whose transcription could be rapidly induced by p53 activation, was significantly upregulated after TBI. Western blot and immunohistochemistrical analyses revealed that the expression of PIDD was gradually increased, reached a peak at 3 days, and then decreased gradually to basal level after brain trauma. Further, double immunofluorescent analysis showed that PIDD was distributed predominantly in neurons, and the number of PIDD-positive neurons was significantly elevated in injured brain cortex. In addition, we found that PIDD was mainly distributed in active caspase-3-positive neurons, implicating a possible involvement of PIDD in the regulation of neuronal apoptosis during TBI. Finally, we showed that the expressions of p53 and Bax were altered correlatively with PIDD after brain trauma, implying that the upregulation of PIDD after TBI might be a result of p53 activation. Taken together, these findings suggested that PIDD might be an important regulator and potential therapeutic target of TBI.
创伤性脑损伤（TBI）引发了一系列复杂的病理事件，最终可能导致神经元凋亡。最近的研究表明，p53 在 TBI 后神经元凋亡和再生中起着至关重要的作用。然而，p53 诱导的 TBI 中神经元凋亡的详细机制在很大程度上仍未被揭示。在这项研究中，我们发现 p53 诱导的死亡结构域蛋白（PIDD）的转录可以被 p53 激活迅速诱导，在 TBI 后显著上调。Western blot 和免疫组化分析显示，PIDD 的表达逐渐增加，在脑创伤后 3 天达到峰值，然后逐渐降至基础水平。此外，双免疫荧光分析显示，PIDD 主要分布在神经元中，损伤皮质中 PIDD 阳性神经元的数量显著增加。此外，我们发现 PIDD 主要分布在活性 caspase-3 阳性神经元中，表明 PIDD 可能参与了 TBI 期间神经元凋亡的调节。最后，我们发现脑外伤后 p53 和 Bax 的表达与 PIDD 呈相关性改变，提示 TBI 后 PIDD 的上调可能是 p53 激活的结果。综上所述，这些发现表明 PIDD 可能是 TBI 的一个重要调节因子和潜在治疗靶点。
