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Overexpression of DJ-1/PARK7, the Parkinson's diseaserelated protein, improves mitochondrial function via Akt phosphorylation on threonine 308 in dopaminergic neuron-like cells.
- Source :
-
European Journal of Neuroscience . May2016, Vol. 43 Issue 10, p1379-1388. 10p. 1 Diagram, 9 Graphs. - Publication Year :
- 2016
-
Abstract
- DJ-1/PARK7, the Parkinson's disease-related protein, plays an important role in mitochondrial function. However, the mechanisms by which DJ-1 affects mitochondrial function are not fully understood. Akt is a promoter of neuron survival and is partly involved in the neurodegenerative process. This research aimed at investigating a possible relationship between DJ-1 and Akt signalling in regulating mitochondrial function in the dopaminergic neuron-like cells SH-SY5Y and PC-12. Overexpression of DJ-1 was firstly validated at both the transcriptional and translational levels after transit transfection with plasmid pcDNA3-Flag-DJ-1. Confocal fluorescence microscopy demonstrated that overexpression of DJ-1 increased the mitochondrial mass, but did not disrupt the mitochondrial morphology. In addition, mitochondrial complex I activity was raised in DJ-1-overexpressing cells, and this rise occurred with an increase in cellular adenosine 50-triphosphate content. Moreover, immunoblotting demonstrated that the levels of phosphoinositide 3-kinase and the total Akt were not altered in DJ-1-overexpressing cells, and nor was the Akt phosphorylation on serine 473 changed. By contrast, Akt phosphorylation on threonine 308 was significantly augmented by overexpression of DJ-1, and the expression of glycogen synthase kinase-3beta, a downstream effector of Akt, was suppressed. In summary, these results suggest that overexpression of DJ-1 improves the mitochondrial function, at least in part, through a mechanism involving Akt phosphorylation on threonine 308. [ABSTRACT FROM AUTHOR]
- Subjects :
- *GENETIC overexpression
*PARKINSON'S disease
*PHOSPHORYLATION
*THREONINE
*MORPHOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 0953816X
- Volume :
- 43
- Issue :
- 10
- Database :
- Academic Search Index
- Journal :
- European Journal of Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 115585201
- Full Text :
- https://doi.org/10.1111/ejn.13216