Plasma membrane ion permeability induced by mutant α-synuclein contributes to the degeneration of neural cells
Plasma membrane ion permeability induced by mutant α-synuclein contributes to the degeneration of neural cells
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DOI：
10.1111/j.1471-4159.2006.03803.x
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发表时间：
2006-05-01
影响因子：
4.7
通讯作者：
Takeda, A
中科院分区：
文献类型：
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作者：
Furukawa, K;Matsuzaki-Kobayashi, M;Takeda, A
α-突触核蛋白的突变导致了一些家族性帕金森病(PD)病例，但α-突触核蛋白促进产生多巴胺的神经元退化的机制尚不清楚。我们报道了表达突变型α-突触核蛋白(A30P和A53T)的人神经细胞具有更高的质膜离子通透性。突变的α-突触核蛋白导致较高的离子渗透性是因为相对较大的孔，大多数阳离子可以非选择性地通过。在表达突变型α-突触核蛋白的细胞中，[Ca~(2+)](I)的基础水平和对膜去极化的Ca~(2+)反应都更强。膜通透性钙离子螯合剂BAPTA-AM对氧化应激有明显的保护作用，而L类钙通道阻断剂(硝苯地平)和N型钙通道阻断剂(欧米茄毒素-GVIA)对细胞无明显保护作用。提示突变型α-突触核蛋白引起的高膜离子通透性可能是帕金森病神经元变性的原因之一。
Mutations in alpha-synuclein cause some cases of familial Parkinson's disease (PD), but the mechanism by which alpha-synuclein promotes degeneration of dopamine-producing neurons is unknown. We report that human neural cells expressing mutant alpha-synuclein (A30P and A53T) have higher plasma membrane ion permeability. The higher ion permeability caused by mutant alpha-synuclein would be because of relatively large pores through which most cations can pass non-selectively. Both the basal level of [Ca2+](i) and the Ca2+ response to membrane depolarization are greater in cells expressing mutant alpha-synuclein. The membrane permeable Ca2+ chelator BAPTA-AM significantly protected the cells against oxidative stress, whereas neither L-type (nifedipine) nor N-type (omega-conotoxin-GVIA) Ca2+ channel blockers protected the cells. These findings suggest that the high membrane ion permeability caused by mutant alpha-synuclein may contribute to the degeneration of neurons in PD.