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Overexpression of PGC-1α influences the mitochondrial unfolded protein response (mtUPR) induced by MPP + in human SH-SY5Y neuroblastoma cells.
- Source :
-
Scientific reports [Sci Rep] 2020 Jun 26; Vol. 10 (1), pp. 10444. Date of Electronic Publication: 2020 Jun 26. - Publication Year :
- 2020
-
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-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 <superscript>+</superscript> 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 <superscript>+</superscript> through LRPPRC signaling, thus maintain mitochondrial homeostasis.
- Subjects :
- ATPases Associated with Diverse Cellular Activities metabolism
Blotting, Western
Cell Line, Tumor
Chaperonin 10 metabolism
Endopeptidase Clp metabolism
Fluorescent Antibody Technique
HSP70 Heat-Shock Proteins metabolism
Humans
Metalloendopeptidases metabolism
Mitochondrial Proteins metabolism
Neoplasm Proteins metabolism
Pregnancy Proteins metabolism
Suppressor Factors, Immunologic metabolism
1-Methyl-4-phenylpyridinium pharmacology
Mitochondria metabolism
Neuroblastoma metabolism
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha metabolism
Unfolded Protein Response drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 32591623
- Full Text :
- https://doi.org/10.1038/s41598-020-67229-6