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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
- 손형진
- Issue Date
- 2011
- Journal Title
- Toxicology Letters
- ISSN
- 0378-4274
- Citation
- Toxicology Letters vol. 202, no. 2, pp. 85 - 92
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- 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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