DJ-1 mediates paraquat-induced dopaminergic neuronal cell death

作者：Kwon Hyun Joo; Heo Jun Young; Shim Jung Hee; Park Ji Hoon; Seo Kang Sik; Ryu Min Jeong; Han Jeong Su; Shong Minho; Son Jin H^*; Kweon Gi Ryang

来源：Toxicology Letters, 2011, 202(2): 85-92.

DOI：10.1016/j.toxlet.2011.01.018

• DJ-1
• Paraquat
• Mitochondrial complex I
• Parkinson's disease

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 land complex I could be a key target in interaction of paraquat toxicity and DJ-1 for giving rise to PD.

• 出版日期2011-4-25
• 单位河北医科大学