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

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

SUBMITTER: Cai Y 

PROVIDER: S-EPMC7320005 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature