title: Anthraquinone derivative exerted hormetic effect on the apoptosis in oxygen-glucose deprivation-induced PC12 cells via ERK and Akt activated Nrf2/HO-1 signaling pathway.
abstract: There were accumulated evidences that agents may attenuate neurological disorders through a hormetic effect. This study was designed to investigate hormetic effect of BME on the oxygen-glucose deprivation (OGD)-induced mitochondrial apoptosis in NGF-differentiated PC12 cells. The effect of BME on the intracellular reactive oxygen species (iROS) formation and pro-survival signals mediated by ERK and Akt as well as transcription factor nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathways was also determined. The present results showed that, at low concentrations, pretreatment with BME triggered stress response by causing ROS production, then, activated survival-promoting signals via ERK and Akt activated Nrf2/HO-1 signaling pathway, resulting in decrease in cytotoxicity induced by the OGD. It may be accepted that mild pretreatment with BME stimulated transient and moderate ROS production, but activated hormetic signals and induced stress responsive genes. In contrast, high concentrations of BME displayed toxic action due to massive ROS production. These results suggested that the effect of BME on the OGD-induced PC12 cells may be hormetic mechanism including induction of oxidative stress and subsequent activation of stress response gene expression.
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, People's Republic of China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, People's Republic of China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Huang
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, People's Republic of China.
authors.forename: Jianhong
authors.initials: J
authors.lastname: Wang
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, People's Republic of China.
authors.forename: Huiling
authors.initials: H
authors.lastname: Song
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, People's Republic of China. Electronic address: cenjuan@henu.edu.cn.
authors.forename: Juan
authors.initials: J
authors.lastname: Cen
authors.affiliation: Key Laboratory of Natural Medicine and Immune Engineering, Henan University, Kaifeng 475001, People's Republic of China. Electronic address: jibiansheng2005@126.com.
authors.forename: Biansheng
authors.initials: B
authors.lastname: Ji
mesh_terms: D000818:Animals; D000880:Anthraquinones / Q000737:chemistry / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002374:Catalase / Q000032:analysis; D015687:Cell Hypoxia; D002470:Cell Survival / Q000187:drug effects; D002867:Chromones / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D051547:Heme Oxygenase-1 / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D063991:Mitochondrial Trifunctional Protein / Q000187:drug effects; D009025:Morpholines / Q000494:pharmacology; D051267:NF-E2-Related Factor 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D013482:Superoxide Dismutase / Q000032:analysis
chemical_list: D000880:Anthraquinones; D002374:Catalase; D002867:Chromones; D048049:Extracellular Signal-Regulated MAP Kinases; D005947:Glucose; D051547:Heme Oxygenase-1; D063991:Mitochondrial Trifunctional Protein; D009025:Morpholines; D051267:NF-E2-Related Factor 2; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051057:Proto-Oncogene Proteins c-akt; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
keywords: BME; Hormetic effect; Nrf2; Oxygen-glucose deprivation; PC12 cells