Department of Information and Communication Sciences, Faculty of Science and Technology, Sophia University, Japan.
Department of Pharmacology, Keio University School of Medicine, Japan.
Biochem Biophys Res Commun. 2018 Jun 2;500(2):470-475. doi: 10.1016/j.bbrc.2018.04.104. Epub 2018 Apr 18.
SUMOylation, a post-translational modification of lysine residues by small ubiquitin-like modifier (SUMO) proteins, has been implicated in the pathogenesis of neurodegenerative disorders including Alzheimer's disease (AD), and in neuron- and astrocyte-specific physiological functions. Global SUMOylation is increased in the AD mouse brain in the pre-plaque-forming stage but returns to wild-type levels in the plaque-bearing stage. To clarify the reason for the transient change in SUMOylation, we analyzed the alteration of global SUMOylation induced by AD-associated cytotoxic stimuli in neurons and astrocytes individually. In neurons, amyloid β42 oligomers induced some but not significant increase in levels of SUMO1-modified proteins. Both hydrogen peroxide and glutamate significantly reduced SUMO1-modified protein levels. These changes were more prominent in neurons than in astrocytes. The opposite effect of Aβ and oxidative/excitotoxic stimuli on SUMO1 modification may cause the pathological stage-associated change in the level of SUMO-modified proteins in the AD mouse brain.
SUMOylation，即赖氨酸残基被小泛素样修饰物（SUMO）蛋白的翻译后修饰，与包括阿尔茨海默病（AD）在内的神经退行性疾病的发病机制有关，也与神经元和星形胶质细胞的特定生理功能有关。在 AD 小鼠大脑的斑块形成前阶段，全局 SUMOylation 增加，但在斑块形成阶段恢复到野生型水平。为了阐明 SUMOylation 短暂变化的原因，我们分析了 AD 相关细胞毒性刺激物在神经元和星形胶质细胞中单独诱导的全局 SUMOylation 的改变。在神经元中，淀粉样β 42 寡聚体诱导 SUMO1 修饰蛋白水平的部分而非显著增加。过氧化氢和谷氨酸均显著降低 SUMO1 修饰蛋白水平。这些变化在神经元中比在星形胶质细胞中更为明显。Aβ 和氧化/兴奋毒性刺激对 SUMO1 修饰的相反作用可能导致 AD 小鼠大脑中 SUMO 修饰蛋白水平与病理阶段相关的变化。
