20C,a new bibenzyl compound, plays a significant role in rotenone-induced oxidative insult
10.3867/j.issn.1000-3002.2017.10.092
- Author:
ZHANG XIAO-LING
1
;
YUAN YU-HE
;
CHEN NAI-HONG
Author Information
1. State Key Laboratory of Bioactive Substances and Functions of Natural Medicines
- Keywords:
20C;
Parkinson disease;
DJ- 1;
Akt;
oxidative stress;
nuclear factor erythroid 2-related factor (Nrf2)
- From:
Chinese Journal of Pharmacology and Toxicology
2017;31(10):1008-1009
- CountryChina
- Language:Chinese
-
Abstract:
20C, a bibenzyl compound isolated from Gastrodia elata, possesses antioxidative properties in PC12 cells, but its in-depth molecular mechanisms against rotenone-induced neurotoxicity remains unknown. Recent studies indicate that without intact DJ- 1, nuclear factor erythroid 2- related factor (Nrf2) protein becomes unstable, and the activity of Nrf2-mediated downstream antioxidant enzymes are thereby suppressed. Therefore, increasing the nuclear translocation of Nrf2 by DJ-1 may present a helpful means for the prevention and treatment of chronic diseases related to oxidative stress. Our results showed that 20C clearly protected PC12 and SH-SY5Y cells against rotenone-induced oxidative injury in a concentration-dependent manner. Furthermore, 20C markedly up-regulated the levels of DJ-1, which in turn activated phosphoinositide-3-kinase (PI3K)/Akt signaling and inhibited glycogen synthase kinase 3β (GSK3β) activation, eventually promoting Nrf2 nuclear translocation and inducing the expression of Nrf2-mediated downstream antioxidative enzymes such as HO-1. The antioxidative effects of 20C could be partially blocked by ShRNA-mediated knockdown of DJ-1 and inhibition of the PI3K/Akt pathways with Akt1/2 kinase inhibitor in PC12 and SH-SY5Y cells, respectively. Conclusively, 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 preventing or alleviating the consequences of PD in the future.
