Cytoprotective effects of 12-oxo phytodienoic acid, a plant-derived oxylipin jasmonate, on oxidative stress-induced toxicity in human neuroblastoma SH-SY5Y cells

被引:48
|
作者
Taki-Nakano, Nozomi [1 ,2 ]
Ohzeki, Hiromitsu [2 ]
Kotera, Jun [2 ]
Ohta, Hiroyuki [3 ,4 ]
机构
[1] Tokyo Inst Technol, Dept Biol Sci, Midori Ku, Yokohama, Kanagawa 2268501, Japan
[2] Mitsubishi Tanabe Pharma Corp, Adv Med Res Labs, Aoba Ku, Yokohama, Kanagawa 2270033, Japan
[3] Tokyo Inst Technol, Ctr Biol Resources & Informat, Midori Ku, Yokohama, Kanagawa 2268501, Japan
[4] Earth Life Sci Inst, Meguro Ku, Tokyo 1528551, Japan
来源
关键词
Plant oxylipins; Jasmonates; OPDA; Nrf2; Oxidative stress; SH-SY5Y; TRANSCRIPTION FACTOR NRF2; HEME OXYGENASE-1; THERAPEUTIC TARGET; GLUTATHIONE METABOLISM; KEAP1/NRF2; PATHWAY; CARNOSIC ACID; ANTIOXIDANT; ACTIVATION; PROTECTS; EXPRESSION;
D O I
10.1016/j.bbagen.2014.09.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 24 hand exposed to hydrogen peroxide (H2O2) for 24 h. 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 phytodienbic 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. General significance: Plant-derived oxylipin OPDA may have the potential to provide protection against oxidative stress-related diseases. (C) 2014 The Authors. Published by Elsevier B.V.
引用
收藏
页码:3413 / 3422
页数:10
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