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

• Published in: Scientific reports Vol. 10; no. 1; p. 10444
• Main Authors: Cai, Yousheng, Shen, Hui, Weng, Huidan, Wang, Yingqing, Cai, Guoen, Chen, Xiaochun, Ye, Qinyong
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 26.06.2020; Nature Publishing Group UK
• Subjects: 1-Methyl-4-phenylpyridinium - pharmacology; 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; Humans; Metalloendopeptidases - metabolism; Mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - metabolism; Movement disorders; MPP; Neoplasm Proteins - metabolism; Neuroblastoma; Neuroblastoma - metabolism; Neuroblastoma cells; Neurodegenerative diseases; Oxidative stress; Parkinson's disease; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha - metabolism; Pregnancy Proteins - metabolism; Protein folding; Proteins; Suppressor Factors, Immunologic - metabolism; Transcription; Unfolded Protein Response - drug effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-020-67229-6

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.