难治性颞叶癫痫患者海马中p53表达升高及MDM2表达降低。
Elevated p53 and lower MDM2 expression in hippocampus from patients with intractable temporal lobe epilepsy.
作者信息
Engel Tobias, Murphy Brona M, Schindler Clara K, Henshall David C
机构信息
Department of Physiology & Medical Physics, Royal College of Surgeons in Ireland, 123 St. Stephen's Green, Dublin 2, Ireland.
出版信息
Epilepsy Res. 2007 Dec;77(2-3):151-6. doi: 10.1016/j.eplepsyres.2007.09.001. Epub 2007 Oct 17.
Recent studies of resected hippocampus from patients with intractable temporal lobe epilepsy (TLE) have yielded biochemical evidence of signalling pathways associated with apoptosis. The tumor suppressor and transcription factor p53 regulates expression of several genes involved in apoptosis. Cellular levels of p53 are regulated in part by murine double minute 2 (MDM2) via ubiquitination and degradation through the proteasome. Presently, we compared expression of p53 and MDM2 in resected hippocampus from patients with intractable TLE to matched autopsy control samples. Western blotting detected significantly higher levels of p53 within TLE samples than controls. MDM2 levels were significantly lower in patient brain and its cleaved form was more abundant. Immunohistochemistry localized elevated p53 to a mainly nuclear distribution in neurons and glia in sections from TLE hippocampus. These data extend other findings on altered expression of genes regulating cell death and survival decisions in human intractable TLE.
最近对难治性颞叶癫痫（TLE）患者切除的海马体进行的研究，已得出与细胞凋亡相关信号通路的生化证据。肿瘤抑制因子及转录因子p53可调节多个参与细胞凋亡的基因的表达。p53的细胞水平部分受小鼠双微体2（MDM2）调控，通过泛素化作用并经蛋白酶体降解。目前，我们将难治性TLE患者切除的海马体中p53和MDM2的表达与匹配的尸检对照样本进行了比较。蛋白质印迹法检测发现，TLE样本中p53的水平显著高于对照组。患者大脑中MDM2的水平显著较低，且其裂解形式更为丰富。免疫组织化学显示，在TLE海马体切片中，p53表达升高，主要定位于神经元和神经胶质细胞的细胞核。这些数据扩展了有关人类难治性TLE中调节细胞死亡和生存决策的基因表达改变的其他研究结果。
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