Overexpression of PGC-1α influences the mitochondrial unfolded protein response (mtUPR) induced by MPP+ in human SH-SY5Y neuroblastoma cells
Overexpression of PGC-1α influences the mitochondrial unfolded protein response (mtUPR) induced by MPP+ in human SH-SY5Y neuroblastoma cells
复制标题
PGC-1α过表达影响人SH-SY5Y神经母细胞瘤细胞中MPP诱导的线粒体未折叠蛋白反应（mtUPR）
DOI：
10.1038/s41598-020-67229-6
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发表时间：
2020-06-26
影响因子：
4.6
通讯作者：
Ye, Qinyong
中科院分区：
文献类型：
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作者：
Cai, Yousheng;Shen, Hui;Ye, Qinyong
帕金森病（PD）是一种常见的运动障碍性疾病，线粒体未折叠蛋白反应（mtUPR）可能直接或间接参与PD的发生、发展，但具体机制尚不清楚。我们建立了PD的多巴胺能神经元样细胞模型，通过PGC-1α的过表达来检测评估参与mtUPR的蛋白酶和分子伴侣的表达，以及PGC-1α和LRPPRC的表达，说明LRPPRC的分布。值得注意的是，SH-SY5Y细胞经MPP+处理后24小时，mtUPR激活达到最大，此时蛋白酶和分子伴侣的蛋白和转录水平达到最大。过表达PGC-1α时蛋白酶和分子伴侣显着增加，说明PGC-1α过表达激活了mtUPR，PGC-1α对SH-SY5Y细胞具有保护作用。 PGC-1α过表达组中PGC-1α和LRPPRC的表达水平显着提高。 LRPPRC在细胞核中显着减少，提示PGC-1α过表达可能通过LRPPRC对线粒体发挥保护作用。我们的研究结果表明，PGC-1α的过度表达可能会激活mtUPR，通过LRPPRC信号减少MPP+诱导的氧化应激损伤，从而维持线粒体稳态。
Parkinson's disease (PD) is a common dyskinesia disease, the mitochondrial unfolded protein response (mtUPR) may be directly or indirectly involved in the occurrence and development of PD, although the exact mechanism is unclear. We established a dopaminergic neuronal-like cell model of PD, by overexpression of PGC-1 alpha to detect evaluate the expression of proteases and molecular chaperones of involved in the mtUPR, as well as the expression of PGC-1 alpha and LRPPRC, illustrated the distribution of LRPPRC. Remarkably, the mtUPR activation reached maximal at 24h after MPP+ treatment in SH-SY5Y cells, which the protein and transcription levels of the proteases and molecular chaperones reached maximal. The proteases and molecular chaperones were significantly increased when overexpressed PGC-1 alpha, which indicated that PGC-1 alpha overexpression activated the mtUPR, and PGC-1 alpha had a protective effect on SH-SY5Y cells. The expression levels of PGC-1 alpha and LRPPRC were significantly improved in the PGC-1 alpha overexpression groups. LRPPRC was markedly reduced in the nucleus, suggesting that PGC-1 alpha overexpression may play a protective role to the mitochondria through LRPPRC. Our finding indicates that overexpression of PGC-1 alpha may activate mtUPR, reducing the oxidative stress injury induced by MPP+ through LRPPRC signaling, thus maintain mitochondrial homeostasis.