Ndfip1 Prevents Rotenone-Induced Neurotoxicity and Upregulation of α-Synuclein in SH-SY5Y Cells.
Ndfip1 Prevents Rotenone-Induced Neurotoxicity and Upregulation of α-Synuclein in SH-SY5Y Cells.
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Ndfip1 防止鱼藤酮诱导的神经毒性和 SH-SY5Y 细胞中 α-突触核蛋白的上调
DOI：
10.3389/fnmol.2020.613404
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发表时间：
2020
影响因子：
4.8
通讯作者：
Xu H
中科院分区：
文献类型：
--
作者：
Liu X;Qu L;Zhang N;Yu X;Xiao Z;Song L;Xie J;Xu H
Nedd 4家族相互作用蛋白1（Ndfip 1）是Nedd 4家族泛素连接酶的接头蛋白。实验结果表明，Ndfip 1在神经系统疾病中具有潜在的神经保护作用。然而，Ndfip 1在帕金森病（PD）中的神经保护作用和潜在机制尚未完全阐明。因此，在本研究中，我们探讨了Ndfip 1对线粒体复合物I抑制剂鱼藤酮在人多巴胺能神经母细胞瘤SH-SY 5 Y细胞系中的神经保护作用，并进一步阐明了其可能的潜在机制。结果表明，鱼藤酮可诱导α-synuclein（α-syn）在mRNA和蛋白水平上表达上调。鱼藤酮处理后24 h，Ndfip 1表达下降。进一步的研究表明，Ndfip 1的高表达可以保护SH-SY 5 Y细胞免受鱼藤酮诱导的神经毒性，并拮抗鱼藤酮诱导的α-syn蛋白水平的升高。此外，Ndfip 1的高表达抑制鱼藤酮诱导的caspase-3蛋白水平的增加和酪氨酸羟化酶（TH）的降低。进一步的研究表明，Ndfip 1对铁调节蛋白1（IRP 1）、转铁蛋白受体1（TfR 1）的蛋白表达无影响，但能拮抗鱼藤酮引起的P62和铁蛋白L蛋白水平的升高。我们的研究结果提供了特异性鉴定Ndfip 1蛋白抑制鱼藤酮诱导的SH-SY 5 Y细胞中α-syn的增加。Ndfip 1可能成为防治PD的一个新的理论药物靶点。
Nedd4 family interacting protein 1 (Ndfip1) is an adaptor of Nedd4-family ubiquitin ligases. Experimental results showed that Ndfip1 had a potential neuroprotective effect in neurology diseases. However, the neuroprotective effect and the underlying mechanisms of Ndfip1 in Parkinson's disease (PD) have not yet been fully elucidated. Therefore, in this study, we explored the neuroprotective effect of Ndfip1 against mitochondrial complex I inhibitor rotenone in a human dopaminergic neuroblastoma SH-SY5Y cell line and further elucidated its possible underlying mechanisms. Our results showed that rotenone could induce the up-regulation of α-synuclein (α-syn) in both mRNA and protein levels. The expression of Ndfip1 decreased at 24 h after rotenone treatment. Further study showed that high expression of Ndfip1 could protect SH-SY5Y cells against rotenone-induced neurotoxicity and antagonize the rotenone-induced increase in α-syn protein levels. In addition, high expression of Ndfip1 inhibited rotenone-induced increase in the protein levels of caspase-3 and decrease in tyrosine hydroxylase (TH). Further study showed that Ndfip1 did not affect the protein expression of iron regulatory protein 1 (IRP1), transferrin receptor 1 (TfR1), while antagonized the increase in protein levels of P62 and ferritin L caused by rotenone. Our findings provide specific identification of Ndfip1 proteins to inhibit the increase of α-syn in rotenone-induced SH-SY5Y cells. Ndfip1 might be a new theoretical drug target for the prevention and treatment of PD.
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影响因子：
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作者：
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