Extracellular α-Synuclein Disrupts Membrane Nanostructure and Promotes S-Nitrosylation-Induced Neuronal Cell Death,Biomacromolecules

当前位置： X-MOL 学术 › Biomacromolecules › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Extracellular α-Synuclein Disrupts Membrane Nanostructure and Promotes S-Nitrosylation-Induced Neuronal Cell Death
Biomacromolecules ( IF 5.5 ) Pub Date : 2018-03-14 00:00:00 , DOI: 10.1021/acs.biomac.7b01727
Roshan Kumar _{1,

2} , Raniki Kumari _{1,

3} , Sanjay Kumar _{1,

2} , Deepak Kumar Jangir ₁ , Tushar Kanti Maiti ₁

Affiliation

α-Synuclein, a major constituent of proteinaceous inclusions named Lewy body, has been shown to be released and taken up by cells, which may facilitate its progressive pathological spreading and neuronal cell death in Parkinson’s disease. However, the pathophysiological effect and signaling cascade initiated by extracellular α-synuclein in cellular milieu are not well understood. Herein we have investigated the perturbations induced by low molecular weight α-synuclein and different types of α-synuclein oligomers in the neuroblastoma SH-SY5Y cells. Atomic force microscopy studies have revealed formation of nanopores and enhanced roughness in the cell surface leading to membrane disruption. The damaged membrane allows altered ionic homeostasis leading to activation of nitric oxide synthase (NOS) machinery releasing burst of nitric oxide. The elevated levels of nitric oxide induces S-nitrosylation of key proteins like Actin, DJ-1, HSP70 UCHL1, Parkin, and GAPDH that alter cytoskeletal network, protein folding machinery, ubiquitin proteasome system inducing apoptosis.

中文翻译：

细胞外α-突触核蛋白破坏膜纳米结构并促进S-亚硝基化诱导的神经元细胞死亡。

已显示α-突触核蛋白（一种称为Lewy体的蛋白质包裹体的主要成分）会被细胞释放并吸收，这可能有助于其在帕金森氏病中进行性病理扩散和神经元细胞死亡。然而，由细胞外α-突触核蛋白在细胞环境中引发的病理生理作用和信号转导级联还没有被很好地理解。在本文中，我们研究了神经母细胞瘤SH-SY5Y细胞中低分子量α-突触核蛋白和不同类型的α-突触核蛋白寡聚物引起的扰动。原子力显微镜研究表明，纳米孔的形成和细胞表面粗糙度的增加导致膜破裂。受损的膜会改变离子稳态，从而导致一氧化氮合酶（NOS）机械活化，释放出一氧化氮。

更新日期：2018-03-14

点击分享查看原文

点击收藏

阅读更多本刊最新论文本刊介绍/投稿指南11