Bondareff W, Matsuyama S S, Dell'Albani P
Department of Psychiatry and the Behavioral Sciences, University of Southern California Medical School, Los Angeles 90033, USA.
J Neurosci Res. 1998 Jun 1;52(5):498-504. doi: 10.1002/(SICI)1097-4547(19980601)52:5<498::AID-JNR2>3.0.CO;2-7.
Neuron-like cells derived from a rat pheochromocytoma cell line (PC12) and differentiated with nerve growth factor produce a paired helical filament (PHF)-like antigen when they are subjected to heat shock (Wallace et al.: Mol Brain Res 19:149-155, 1993). It accumulates in a localized region of the perinuclear cytoplasm and reacts with monoclonal antitau antibodies, which identify epitopes in the N- and C-terminal halves and the microtubule-binding domain of tau protein. The observed profile of immunoreactivity suggests the presence of full-length and C-terminally truncated tau in a region of perinuclear cytoplasm in which no structurally intact PHFs could be demonstrated by conventional transmission electron microscopy. The accumulated tau protein colocalized with antibodies raised against mitochondrial outer membrane proteins and was associated with the presence of numerous mitochondrial profiles that were demonstrated with electron microscopy. Because differentiated PC12 cells pretreated with colcemid or Taxol prior to heat shock fail to exhibit perinuclear PHF-like immunoreactivity, the reported response to heat shock appears to require an intact system of intracellular microtubules. This PC12 system provides a model in which the metabolic and molecular biological underpinnings of neuronal degeneration in Alzheimer's disease can be manipulated. The system may eventually be applicable to the development of pharmaceutical agents that interfere with formation and/or degeneration of PHF-tau in Alzheimer's disease.
源自大鼠嗜铬细胞瘤细胞系（PC12）并经神经生长因子分化的神经元样细胞，在受到热休克时会产生一种成对螺旋丝（PHF）样抗原（华莱士等人：《分子脑研究》19:149 - 155，1993）。它积聚在核周细胞质的一个局部区域，并与单克隆抗tau抗体发生反应，这些抗体可识别tau蛋白N端和C端以及微管结合结构域中的表位。观察到的免疫反应谱表明，在核周细胞质区域存在全长和C端截短的tau，而传统透射电子显微镜未能在该区域证实存在结构完整的PHF。积累的tau蛋白与针对线粒体外膜蛋白产生的抗体共定位，并与电子显微镜显示的大量线粒体轮廓相关。由于在热休克前用秋水仙酰胺或紫杉醇预处理的分化PC12细胞未表现出核周PHF样免疫反应，所报道的对热休克的反应似乎需要完整的细胞内微管系统。这个PC12系统提供了一个模型，在其中可以操控阿尔茨海默病中神经元变性的代谢和分子生物学基础。该系统最终可能适用于开发干扰阿尔茨海默病中PHF - tau形成和/或变性的药物制剂。
