Hamanaka Taichi, Nishizawa Keiko, Sakasegawa Yuji, Kurahashi Hiroshi, Oguma Ayumi, Teruya Kenta, Doh-Ura Katsumi
Department of Neurochemistry, Tohoku University Graduate School of Medicine, 2-1 Seiryocho, Sendai 980-8575, Japan.
Biochem Biophys Rep. 2015 Jul 17;3:32-37. doi: 10.1016/j.bbrep.2015.07.009. eCollection 2015 Sep.
No remedies for prion disease have been established, and the conversion of normal to abnormal prion protein, a key event in prion disease, is still unclear. Here we found that substances in beetle grub hemolymph, after they were browned by aging for a month or heating for hours, reduced abnormal prion protein (PrP) levels in RML prion-infected cells. Active anti-prion components in the hemolymph were resistant to protease treatment and had molecular weights larger than 100 kDa. Aminoguanidine treatment of the hemolymph abolished its anti-prion activity, suggesting that Maillard reaction products are enrolled in the activity against the RML prion. However, levels of abnormal PrP in RML prion-infected cells were not decreased by incubation with the Maillard reaction products formed by amino acids or bovine serum albumin. The anti-prion components in the hemolymph modified neither cellular or cell-surface PrP levels nor lipid raft or autophagosome levels. The anti-prion activity was not observed in cells infected with 22 L prion or Fukuoka-1 prion, suggesting the anti-prion action is prion strain-dependent. Although the active components of the hemolymph need to be further evaluated, the present findings imply that certain specific chemical structures in the hemolymph, but not chemical structures common to all Maillard reaction products, are involved in RML prion formation or turnover, without modifying normal PrP expression. The anti-prion components in the hemolymph are a new tool for elucidating strain-dependent prion biology.
目前尚未确立针对朊病毒疾病的治疗方法，而正常朊病毒蛋白向异常朊病毒蛋白的转化作为朊病毒疾病中的关键事件，仍不清楚。在此，我们发现，经一个月老化或数小时加热而褐变后的甲虫幼虫血淋巴中的物质，可降低感染RML朊病毒的细胞中异常朊病毒蛋白（PrP）的水平。血淋巴中的活性抗朊病毒成分对蛋白酶处理具有抗性，且分子量大于100 kDa。用氨基胍处理血淋巴可消除其抗朊病毒活性，这表明美拉德反应产物参与了针对RML朊病毒的活性。然而，用氨基酸或牛血清白蛋白形成的美拉德反应产物孵育感染RML朊病毒的细胞后，异常PrP的水平并未降低。血淋巴中的抗朊病毒成分既未改变细胞内或细胞表面的PrP水平，也未改变脂筏或自噬体水平。在感染22L朊病毒或福冈-1朊病毒的细胞中未观察到抗朊病毒活性，这表明抗朊病毒作用具有朊病毒株依赖性。尽管血淋巴中的活性成分需要进一步评估，但目前的研究结果表明，血淋巴中的某些特定化学结构，而非所有美拉德反应产物共有的化学结构，参与了RML朊病毒的形成或周转，而不改变正常PrP的表达。血淋巴中的抗朊病毒成分是阐明朊病毒株依赖性生物学的一种新工具。
