Morandi A, Los B, Osofsky L, Autilio-Gambetti L, Gambetti P
Division of Neuropathology, Case Western Reserve University, Cleveland, Ohio 44106.
Prog Clin Biol Res. 1989;317:819-27.
Ubiquitin (Ub) and Heat Shock Proteins (HSP) are believed to act jointly in the recovery process of an organism exposed to a stress. Ubiquitin has been recently found associated with paired helical filaments (PHF) in tangles of Alzheimer disease (AD) and Progressive Supranuclear Palsy (PSP) and with abnormal structures in other degenerative diseases, suggesting a role in their pathogenesis. To elucidate the mechanism of action, functions and relationship of Ub and the HSPs in the nervous tissue, we applied physical or chemical stress to neurons in culture. Rat dorsal root ganglia (DRG) explants were exposed either to aluminum lactate or to heat shock, the stress response was then studied with biochemical and immunological methods. The results show a clear dissociation in the formation of Ub-conjugates and the induction of the major HSPs, depending on the type of stress conditions.
泛素(Ub)和热休克蛋白(HSP)被认为在生物体遭受应激后的恢复过程中共同发挥作用。最近发现泛素与阿尔茨海默病(AD)和进行性核上性麻痹(PSP)缠结中的双螺旋丝(PHF)以及其他退行性疾病中的异常结构相关,提示其在发病机制中起作用。为了阐明泛素和热休克蛋白在神经组织中的作用机制、功能及关系,我们对培养的神经元施加物理或化学应激。将大鼠背根神经节(DRG)外植体暴露于乳酸铝或热休克,然后用生化和免疫方法研究应激反应。结果表明,根据应激条件的类型,泛素结合物的形成与主要热休克蛋白的诱导存在明显的分离。