title: Transcriptional upregulation centra of HO-1 by EGB via the MAPKs/Nrf2 pathway in mouse C2C12 myoblasts.
abstract: Long-term abuse of alcohol results in chronic alcoholic myopathy which is associated with increased oxidative stress. Ginkgo biloba extract (EGB) is widely used as a therapeutic agent to treat certain cardiovascular and neurological disorders. Although EGB is known to possess antioxidant functions and potent cytoprotective effects, its protective mechanism on alcohol-induced oxidative damage in C2C12 myoblasts remains unclear. In this study, we investigated the cytoprotective mechanisms of EGB against alcohol-derived oxidative stress in mouse C2C12 myoblasts. Challenge with alcohol (100mM) caused an increase in intracellular reactive oxygen species in mouse C2C12 myoblasts, which was not alleviated by treatment with EGB. These results indicate that EGB does not seem to act as an ROS scavenger in this experimental model. Additionally, EGB produced activation of ERK and JNK [two major mitogen-activated protein kinases (MAPKs)], an increase in the nuclear level of nuclear factor erythroid-2-related factor 2 (Nrf2) and upregulation of heme oxygenase-1 (HO-1, a stress-responsive protein with antioxidant function). Pretreatment with inhibitors of MAPKs PD98059 (a specific inhibitor of ERK), SP600125 (a specific inhibitor of JNK) abolished both EGB-induced Nrf2 nuclear translocation and HO-1 up-regulation. We conclude that EGB confers cytoprotective effects from oxidative stress induced by alcohol in mouse C2C12 myoblasts depend on transcriptional upregulation of HO-1 by EGB via the MAPKs/Nrf2 pathway.
authors.affiliation: Department of Neurology, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Central Laboratory, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
authors.forename: Meiling
authors.initials: M
authors.lastname: Luo
authors.affiliation: Department of Neurology, Affiliated Dalian Central Hospital of Dalian Medical University, Dalian 116033, Liaoning Province, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Histology and Embryology, Colleges of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning Province, China.
authors.forename: Lijun
authors.initials: L
authors.lastname: Yu
authors.affiliation: Department of Histology and Embryology, Colleges of Basic Medical Sciences, Dalian Medical University, Dalian 116044, Liaoning Province, China. Electronic address: hychu2013@163.com.
authors.forename: Haiying
authors.initials: H
authors.lastname: Chu
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002460:Cell Line; D000431:Ethanol / Q000633:toxicity; D020441:Ginkgo biloba; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D032446:Myoblasts / Q000187:drug effects / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D008565:Membrane Proteins; D051267:NF-E2-Related Factor 2; D010936:Plant Extracts; D017382:Reactive Oxygen Species; D000431:Ethanol; D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse; D020928:Mitogen-Activated Protein Kinases
keywords: Alcohol; C2C12 myoblasts; Ginkgo biloba extract; Heme oxygenase-1