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DJ-1 mediates paraquat-induced dopaminergic neuronal cell death

Title
DJ-1 mediates paraquat-induced dopaminergic neuronal cell death
Authors
Kwon H.J.Heo J.Y.Shim J.H.Park J.H.Seo K.S.Ryu M.J.Han J.S.Shong M.Son J.H.Kweon G.R.
Ewha Authors
손형진
SCOPUS Author ID
손형진scopus
Issue Date
2011
Journal Title
Toxicology Letters
ISSN
0378-4274JCR Link
Citation
vol. 202, no. 2, pp. 85 - 92
Indexed
SCI; SCIE; SCOPUS WOS scopus
Abstract
There are two causes of Parkinson's disease (PD): environmental insults and genetic mutations of PD-associated genes. Environmental insults and genetic mutations lead to mitochondrial dysfunction, and a combination of mitochondrial dysfunction and increased oxidative stress in dopaminergic neurons is thought to contribute to the pathogenesis of PD. Among the PD-associated genes, DJ-1 acts as a redox sensor for oxidative stress and has been also proposed to maintain mitochondrial complex I activity. To understand molecular functions of DJ-1 in the cell, we have generated DJ-1 null cells from the DJ-1(-/-) mouse embryos. Using these null cells, we investigated the susceptibility to an environmental toxin, paraquat, which is known to inhibit mitochondrial complex I. Interestingly, we found that DJ-1 null cells showed a resistance to paraquat-induced apoptosis, including reduced poly (ADP-ribose) polymerase and procaspase-3. Also DJ-1 null cells generated less superoxide than SN4741 cells by paraquat treatment. Consistent with the reduced paraquat sensitivity, DJ-1 null cells showed reduced complex I activity, which was partially rescued by ectopic DJ-I expression. In summary, our results suggest that DJ-1 is critical to maintain mitochondrial complex I and complex I could be a key target in interaction of paraquat toxicity and DJ-1 for giving rise to PD. © 2011 Elsevier Ireland Ltd.
DOI
10.1016/j.toxlet.2011.01.018
Appears in Collections:
약학대학 > 약학과 > Journal papers
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