کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
2590081 | 1131723 | 2009 | 6 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Subchronic exposure to arsenic decreased Sdha expression in the brain of mice Subchronic exposure to arsenic decreased Sdha expression in the brain of mice](/preview/png/2590081.png)
Exposure of arsenic (As) elevates reactive oxygen species (ROS) level, which is supposed to be a molecular mechanism of As neurotoxicity. Mitochondria are the major source of ROS. However, the mechanism of the ROS generation induced by As remains unclear. To provide target evidence for exploring the molecular mechanism of As-induced neurotoxicity, 8-hydroxy-2-deoxyguanosine (8-OHdG) as an oxidative damage biomarker was examined, and the critical gene expression profiles related to mitochondrial respiratory chain were analyzed by GeneChip in mice exposed to As2O3 subchronically. Our results showed that immunoreactivity of 8-OHdG increased remarkably. Succinate dehydrogenase subunit A (Sdha), ubiquinol-cytochrome c oxidoreductase gene (Uqcr), cytochrome oxidase genes (Cox6a2, Cox17) and ATP Synthase genes (Atp5a1, Atp5g1, Atpif1) were down-regulated in brain cells of mice exposed to As. We further analyzed the influence of As on brain Sdha expression using Western blot method. The quantity of Sdha band and the corresponding succinate dehydrogenase (SDH) activity in the group exposed to 4 ppm As2O3 significantly decreased compared to the 1 ppm or control group, agreeing well with the gene microarray result. These results indicate that subchronic exposure to As induces down-regulation of Sdha expression and inhibition of SDH activity in brain tissue. They also suggest that the Sdha as complex II subunit may be a molecular target for As in mitochondria. Furthermore, the intervening experiment showed that the coadministered antioxidants taurine or vitamin C scavenging ROS in vivo partly rescued Sdha expression. It implies that the increased level of ROS by As may also be a factor in the disrupting Sdha expression in brain tissue of mice exposed to As.
Journal: NeuroToxicology - Volume 30, Issue 4, July 2009, Pages 538–543