Free -radical generation by amyloid p protein and the protective effect by laminin against amyloid β-protein induced toxicity

淀粉样p蛋白产生自由基以及层粘连蛋白对淀粉样β蛋白诱导的毒性的保护作用

• 批准号: 15591235
• 负责人: HAYASHI Yoshihito
• 金额: $ 1.92万
• 依托单位: University of Miyazaki (2004)宮崎医科大学 (2003)
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591235/
• 关键词: β amyloid; laminin; free radical; NMDA

We investigated the inhibitory effect by laminin, which is one of the extracellular matrix components, against beta amyloid(Aβ) induced free radicals by electron paramagnetic resonance(EPR) using PC12 cells with two kinds of spin trap, 5,5-dimethyl-1-pyrroline-N-oxide ; DMPO, α-(4-pyridyl-1-oxide)-N-tert-butylnitrone ; POBN respectively. We investigated two kinds of experiment to clear the mechanism how laminin shows the protection against Aβ. At first, EPR measurement was performed to see whether or not laminin directly inhibit Aβ induced free radicals, Aβ was mixed with laminin and the solution was added to PC12 cells. The second, EPR measurement was also performed to see whether or not the cells which attached laminin get strengthened their defense function.The free radical production was reduced when Aβ was mixed with laminin and the cell viability also increased compared with Aβ only added to the cells, though there was no difference in generating free radicals between cells which were attached with laminin for 24hrs before Aβ addition and cells which did not attach laminin for 24hrs. Therefore we concluded that laminin has neuroprotective ability and its protective effect against Aβ induced free radical generation is due to possibly direct reaction with Aβ.

我们用电子顺磁共振技术研究了细胞外基质成分层粘连蛋白对β-淀粉样蛋白(A-β)诱导的自由基的抑制作用。方法：分别用5，5-二甲基-1-吡咯啉-N-氧化物、α-(4-吡啶-1-氧化物)-N-叔丁基硝酮和POBN两种自旋陷阱。我们研究了两种实验，以明确层粘连蛋白对Aβ的保护机制。首先，将层粘连蛋白与Aβ混合后加入PC12细胞中，观察层粘连蛋白是否能直接抑制Aβ诱导的自由基。Aβ与层粘连蛋白混合作用后，细胞存活率较单独加入Aβ时有所增加，但在Aβ加入前24小时与未附着层粘连蛋白的细胞相比，两者在自由基产生方面无明显差异。因此，我们认为层粘连蛋白具有神经保护作用，其对Aβ诱导的自由基产生的保护作用可能是通过与Aβ的直接反应实现的。

项目成果

EPR evidence of hydroxyl radical generation as an initiator of lipid peroxidation in amyloid β-protein-stimulated PC12 cells

EPR 证据表明，β-淀粉样蛋白刺激的 PC12 细胞中羟基自由基的产生是脂质过氧化的引发剂

• 发表时间: 2004
• 期刊: Brain Research 1025
• 作者: Yoshihito Hayashi;Yuto Ueda;Akira Nakajima;Yoshio Mistuyama
• 通讯作者: Yoshio Mistuyama

EPR evidence of hydroxyl radical generation as an initiator of lipid paroxidation in amyloid β-protein-stimulated PC12 cells

EPR 证据表明，β-淀粉样蛋白刺激的 PC12 细胞中羟基自由基的产生是脂质三氧化二氮的引发剂

• 发表时间: 2004
• 期刊: Brain Research 1025
• 作者: Yoshihito Hayashi;Yuto Ueda;Akira Nakajima;Yoshio Mitsuyama
• 通讯作者: Yoshio Mitsuyama