Takagane Kurara, Nojima Jun, Mitsuhashi Hiroaki, Suo Satoshi, Yanagihara Dai, Takaiwa Fumio, Urano Yasuomi, Noguchi Noriko, Ishiura Shoichi
a Department of Biological Sciences, Graduate School of Science , The University of Tokyo , Tokyo , Japan.
Biosci Biotechnol Biochem. 2015;79(6):912-8. doi: 10.1080/09168451.2014.1002449. Epub 2015 Jan 23.
According to the amyloid hypothesis, amyloid β accumulates in brains with Alzheimer's disease (AD) and triggers cell death and memory deficit. Previously, we developed a rice Aβ vaccine expressing Aβ, which reduced brain Aβ levels in the Tg2576 mouse model of familial AD. We used senescence-accelerated SAMP8 mice as a model of sporadic AD and investigated the relationship between Aβ and oxidative stress. Insoluble Aβ and 4-hydroxynonenal (4-HNE) levels tended to be reduced in SAMP8 mice-fed the rice Aβ vaccine. We attempted to clarify the relationship between oxidative stress and Aβ in vitro. Addition of Aβ peptide to the culture medium resulted in an increase in 4-HNE levels in SH-SY5Y cells. Tg2576 mice, which express large amounts of Aβ in their brain, also exhibited increased 4-HNE levels; this increase was inhibited by the Aβ vaccine. These results indicate that Aβ induces oxidative stress in cultured cells and in the mouse brain.
根据淀粉样蛋白假说，淀粉样β蛋白在阿尔茨海默病（AD）患者的大脑中积累，引发细胞死亡和记忆缺陷。此前，我们开发了一种表达Aβ的水稻Aβ疫苗，该疫苗可降低家族性AD的Tg2576小鼠模型脑中的Aβ水平。我们使用衰老加速的SAMP8小鼠作为散发性AD的模型，研究了Aβ与氧化应激之间的关系。喂食水稻Aβ疫苗的SAMP8小鼠中，不溶性Aβ和4-羟基壬烯醛（4-HNE）水平趋于降低。我们试图在体外阐明氧化应激与Aβ之间的关系。向培养基中添加Aβ肽会导致SH-SY5Y细胞中4-HNE水平升高。在脑中大量表达Aβ的Tg2576小鼠也表现出4-HNE水平升高；这种升高被Aβ疫苗抑制。这些结果表明，Aβ在培养细胞和小鼠脑中诱导氧化应激。
