title: Cytoprotective effects of 12-oxo phytodienoic acid, a plant-derived oxylipin jasmonate, on oxidative stress-induced toxicity in human neuroblastoma SH-SY5Y cells.
abstract: BACKGROUND
  Jasmonates are plant lipid-derived oxylipins that act as key signaling compounds when plants are under oxidative stress, but little is known about their functions in mammalian cells. Here we investigated whether jasmonates could protect human neuroblastoma SH-SY5Y cells against oxidative stress-induced toxicity.
  
  
  METHODS
  The cells were pretreated with individual jasmonates for 24h and exposed to hydrogen peroxide (H2O2) for 24h. Before the resulting cytotoxicity, intracellular reactive oxygen species (ROS) levels, and mitochondrial membrane potential were measured. We also measured intracellular glutathione (GSH) levels and investigated changes in the signaling cascade mediated by nuclear factor erythroid 2-related factor 2 (Nrf2) in cells treated with 12-oxo phytodienoic acid (OPDA).
  
  
  RESULTS
  Among the jasmonates, only OPDA suppressed H2O2-induced cytotoxicity. OPDA pretreatment also inhibited the H2O2-induced ROS increase and mitochondrial membrane potential decrease. In addition, OPDA induced the nuclear translocation of Nrf2 and increased intracellular GSH level and the expression of the Nrf2-regulated phase II antioxidant enzymes heme oxygenase-1, NADPH quinone oxidoreductase 1, and glutathione reductase. Finally, the cytoprotective effects of OPDA were reduced by siRNA-induced knockdown of Nrf2.
  
  
  CONCLUSIONS
  These results demonstrated that among jasmonates, only OPDA suppressed oxidative stress-induced death of human neuroblastoma cells, which occurred via activation of the Nrf2 pathway.
  
  
  CONCLUSIONS
  Plant-derived oxylipin OPDA may have the potential to provide protection against oxidative stress-related diseases.
authors.affiliation: Department of Biological Sciences, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan; Advanced Medical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan. Electronic address: takinakano.n.aa@m.titech.ac.jp.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Taki-Nakano
authors.affiliation: Advanced Medical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Hiromitsu
authors.initials: H
authors.lastname: Ohzeki
authors.affiliation: Advanced Medical Research Laboratories, Mitsubishi Tanabe Pharma Corporation, 1000, Kamoshida-cho, Aoba-ku, Yokohama 227-0033, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kotera
authors.affiliation: Center for Biological Resources and Informatics, Tokyo Institute of Technology, 4259-B-65 Nagatsuta-cho, Midori-ku, Yokohama 226-8501, Japan; Earth-Life Science Institute, Ookayama, Meguro-ku, Tokyo 152-8551, Japan. Electronic address: ohta.h.ab@m.titech.ac.jp.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Ohta
keywords: Jasmonates; Nrf2; OPDA; Oxidative stress; Plant oxylipins; SH-SY5Y