ILSONG Institute of Life Science, Hallym University, Anyang, Gyeonggi-do 431-060, Republic of Korea.
Biochem Biophys Res Commun. 2011 Jan 14;404(2):638-45. doi: 10.1016/j.bbrc.2010.12.030. Epub 2010 Dec 10.
To investigate the in vivo functions of normal prion protein (PrP) in Drosophila, we utilized characterized transgenic flies expressing ³(F)⁴-tagged mouse PrP (Mo-PrP³(F)⁴). The neurotoxicity of pathogenic Machado-Joseph Disease (MJD) glutamine (Q) 78 and 127Q proteins were enhanced by the co-expression of Mo-PrP³(F)⁴in the fly eyes, while the eyes of controls flies and flies expressing Mo-PrP³(F)⁴) alone or together with MJD-Q27 or 20Q proteins did not show any defect. Susceptibilities to H₂O₂, paraquat, and Dithiothreitol (DTT) were altered in Mo-PrP³(F)⁴ flies. In addition, Mo-PrP³(F)⁴ flies were significantly more susceptible to the perturbation of autophagy signaling by an autophagy inhibitor, 3-methyladenine (3-MA), and inducer, LiCl. Taken together, our data suggest that Mo-PrP³(F)⁴ may enhance the neurotoxicity of pathogenic Poly-Q proteins by perturbing oxidative and autophagy signaling.
为了研究正常朊病毒蛋白（PrP）在果蝇体内的功能，我们利用表达 ³(F)⁴ 标记的小鼠 PrP（Mo-PrP³(F)⁴）的特征性转基因果蝇进行了研究。致病性 Machado-Joseph 病（MJD）谷氨酰胺（Q）78 和 127Q 蛋白的神经毒性通过在果蝇眼睛中共同表达 Mo-PrP³(F)⁴而增强，而对照果蝇眼睛和单独表达 Mo-PrP³(F)⁴或与 MJD-Q27 或 20Q 蛋白共同表达的果蝇眼睛没有显示任何缺陷。Mo-PrP³(F)⁴ 果蝇对 H₂O₂、百草枯和 Dithiothreitol（DTT）的敏感性发生了改变。此外，Mo-PrP³(F)⁴ 果蝇对自噬抑制剂 3-甲基腺嘌呤（3-MA）和诱导剂 LiCl 引起的自噬信号的干扰更加敏感。综上所述，我们的数据表明，Mo-PrP³(F)⁴ 可能通过扰乱氧化和自噬信号来增强致病性 Poly-Q 蛋白的神经毒性。
