BAX protein-immunoreactivity in midbrain neurons of Parkinson's disease patients

BAX protein-immunoreactivity in midbrain neurons of Parkinson's disease patients
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DOI:
10.1016/j.brainresbull.2003.08.005
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发表时间:
2003-11-15
影响因子:
3.8
通讯作者:
Torres, G
Torres, G
中科院分区:
医学3区
文献类型:
--
作者:
Horowitz, JM;Pastor, DM;Torres, G

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细胞凋亡与帕金森病(PD)的病理生理学有关。启动细胞死亡的信号通路组分高度集中在脆弱的黑质(SN)神经元中,因此可能导致多巴胺细胞的无情死亡。在这里,我们报告的分布和组织模式的促凋亡蛋白BAX在帕金森病患者的大脑。从控制和PD患者的SN材料的冠状切片(60 μ m)在所有检查的情况下,表现出相同的表达Bax免疫反应性(IR)。BAX-IR阳性的神经元表现出离散的细胞质和树突标记,这是显着散布与以前未识别的轴突球状体样夹杂物。直接比较显示,富含BAX的包涵体的聚集存在差异,帕金森病患者的大脑中含有比对照病例更多的SN包涵体。通过对SN提取物进行免疫印迹分析证实中脑神经元的BAX表达,其显示约21 kDa的特异性条带,这与天然BAX的已知分子量一致。这些结果表明,细胞凋亡或程序性细胞死亡可能在特发性PD中起间接作用。(C)2003年爱思唯尔公司All rights reserved.
Apoptosis has been implicated in the pathophysiology of Parkinson's disease (PD). Components of signaling pathways that initiate cell death are highly concentrated in vulnerable substantia nigra (SN) neurons and may therefore contribute to the relentless demise of dopamine cells. Here, we report the distribution and organizational pattern of the pro-apoptotic protein BAX in the parkinsonian brain. Coronal sections (60 mum) of SN material from control and PD patients showed identical expression of BAX-immunoreactivity (IR) in all cases examined. Neurons positive for BAX-IR exhibited a discrete cytoplasmic and dendritic labeling that was conspicuously interspersed with previously unrecognized axonal spheroid-like inclusions. Direct comparisons revealed a difference in the aggregation of BAX-rich inclusions, with the parkinsonian brain containing more SN inclusions than control cases. BAX expression by midbrain neurons was confirmed by immunoblot analysis on SN extracts showing a specific band of approximately 21 kDa, which is consistent with the known molecular weight of native BAX. These results suggest that apoptosis or programmed cell death may play an indirect role in idiopathic PD. (C) 2003 Elsevier Inc. All rights reserved.