Journal
FREE RADICAL BIOLOGY AND MEDICINE
Volume 45, Issue 6, Pages 820-825Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.freeradbiomed.2008.06.007
Keywords
Parkinson's disease; MPP+; ubiquitin-proteasome system; mitochondria; reactive oxygen species; mitochondrial DNA-depleted cells
Funding
- GAPI of Faculdade de Medicina da Universidade de Coimbra, Portugal
- Parkinson's Disease Foundation of the Heartland (USA)
Ask authors/readers for more resources
The cellular mechanisms that may underlie the death of dopaminergic neurons in Parkinson's disease are ubiquitin-proteasomal system (UPS) impairment, mitochondrial dysfunction. and oxidative stress. The goal of this work was to elucidate the correlation between mitochondrial dysfunction and UPS impairment, focusing Oil the role of oxidative stress. Our data revealed that mitochondria-DNA-depleted cells (rho 0) are compromised at the mitochondrial and UPS levels and also show an alteration of the oxidative status. In parental cells (rho+), MPP+ induced a clear inhibition of complex I activity, as well as an increase in ubiquitinylated protein levels, which was not observed in cells treated with lactacystin. Moreover, MPP+ induced a decreased in the 20S chymotrypsin-like and peptidyl-glutamyl peptide hydrolytic-like proteolytic activities after 24 h of exposure. RIDS Production Was increased in rho+ cells treated with MPP+ or lactacystin, at early treatment periods. MPP+ induced an increase in carbonyl group formation in rho+ cells. The results suggest that a mitochondrial alteration leads to an imbalance in the cellular oxidative status, inducing a proteasomal deregulation, which may exacerbate protein aggregation, and consequently degenerative events. (C) 2008 Elsevier Inc. All rights reserved.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available