Abstract
Parkinson disease (PD) is reported to be caused by an interaction between genetic and environmental factors. Fewer studies clarified environmental factors. Rotenone, a pesticide, is recently highlighted because rotenone treatment to animals produces many features of PD including behavioral abnormalities, selective degeneration of nigral dopaminergic neurons and formation of ubiquitin-positive aggregates in nigral neurons. We investigated the neurotoxicities of rotenone using PC12 cells. Rotenone induced PC12 cell to die in concentration dependent manner. Degenerating PC12 cells were stained by terminal deoxynucleotidyl transferase mediated dUTP nick end labeling and anti-active caspase3 antibody, indicating that the degenerating PC12 undergo cell death via apoptosis. The endoplasmic reticulum (ER) stress were found to be involved in this rotenone-induced apoptosis because upregulation of CHOP and activation of Jun-N-terminal kinase (JNK), ER stress activated substrates, were observed. Upregulation of mRNA of BiP, an ER-specific chaperone, and splicing of the mRNA of the X box binding protein were observed, indicating the occurrence of the unfolded protein response (UPR). Prominent production of reactive oxygen species (ROS) was observed after rotenone exposure. Preincubation of resveratrol, an antioxidant polyphenol included in red wine, reduced the rotenone-induced ROS and UPR. The viability of PC12 cells was increased by resveratrol. These data suggested that resveratrol has preventive effects on PD. [J Physiol Sci. 2007;57 Suppl:S114]
