Journal Article

Overexpression of PGC-1α influences the mitochondrial unfolded protein response (mtUPR) induced by MPP+ in human SH-SY5Y neuroblastoma cells

Cai, Yousheng, Cai, Guoen, Ye, Qinyong, Wang, Yingqing, Shen, Hui, Chen, Xiaochun, Weng, Huidan

2020

Overview

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-1α to detect evaluate the expression of proteases and molecular chaperones of involved in the mtUPR, as well as the expression of PGC-1α and LRPPRC, illustrated the distribution of LRPPRC. Remarkably, the mtUPR activation reached maximal at 24 h 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-1α, which indicated that PGC-1α overexpression activated the mtUPR, and PGC-1α had a protective effect on SH-SY5Y cells. The expression levels of PGC-1α and LRPPRC were significantly improved in the PGC-1α overexpression groups. LRPPRC was markedly reduced in the nucleus, suggesting that PGC-1α overexpression may play a protective role to the mitochondria through LRPPRC. Our finding indicates that overexpression of PGC-1α may activate mtUPR, reducing the oxidative stress injury induced by MPP + through LRPPRC signaling, thus maintain mitochondrial homeostasis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 1-Methyl-4-phenylpyridinium - pharmacology / 13/1 / 13/51 / 14/19 / 14/63 / 38/22 / 38/77 / 631/378/340 / 692/617/375/1718 / ATPases Associated with Diverse Cellular Activities - metabolism / Blotting, Western / Cell Line, Tumor / Chaperones / Chaperonin 10 - metabolism / Dopamine receptors / Dyskinesia / Endopeptidase Clp - metabolism / Fluorescent Antibody Technique / Homeostasis / HSP70 Heat-Shock Proteins - metabolism / Humanities and Social Sciences / Humans / Metalloendopeptidases - metabolism / Mitochondria / Mitochondria - metabolism / Mitochondrial Proteins - metabolism / Movement disorders / MPP / multidisciplinary / Neoplasm Proteins - metabolism / Neuroblastoma / Neuroblastoma - metabolism / Neuroblasts / Neurodegenerative diseases / Oxidative stress / Parkinson's disease / Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism / Pregnancy Proteins - metabolism / Protein folding / Proteins / Science / Science (multidisciplinary) / Suppressor Factors, Immunologic - metabolism / Transcription / Unfolded Protein Response - drug effects