主催: The Japanese Pharmacological Society, The Japanese Society of Clinical Pharmacology
会議名: WCP2018 (18th World Congress of Basic and Clinical Pharmacology)
開催地: Kyoto
開催日: 2018/07/01 - 2018/07/06
Oxidative stress is an important factor in the pathogenesis of Parkinson's disease (PD). In the past, we revealed that 20C, a bibenzyl compound extracted from Gastrodia elata, has properties of antioxygenation, but its intrinsic molecular mechanism of resisting neurotoxicity induced by rotenone is still unclear. Current research indicate that nuclear factor erythroid 2-related factor (Nrf2) protein becomes precarious without intact DJ-1, and the capability of downstream enzymes is then restrained. In this research, we showed that 20C remarkably protected SH-SY5Y and PC12 cells from oxidative injury induced by rotenone. Furthermore, 20C remarkably up-regulated the levels of DJ-1, which in turn activated phosphoinositide-3-kinase (PI3K)/Akt signaling and inhibited glycogen synthase kinase 3b (GSK3b) activation, eventually promoted the nuclear translocation of Nrf2 and induced the expression of hemeoxygenase-1 (HO-1). We could partially block the antioxidant effects of 20C by knockdown of DJ-1 mediated by shRNA and inhibition of the PI3K/Akt pathways with Akt1/2 kinase inhibitor, respectively. In a conclusion, our findings confirm that DJ-1 is necessary for 20C-mediated protection against rotenone-induced oxidative damage, at least in part, by activating PI3K/Akt signaling, and subsequently enhancing the nuclear accumulation of Nrf2. The findings from our investigation suggest that 20C should be developed as a novel candidate for alleviating the consequences of PD in the future.