title: Involvement of IGF-1 receptor signaling pathway in the neuroprotective effects of Icaritin against MPP(+)-induced toxicity in MES23.5 cells.
abstract: Icaritin, a natural derivative of Icariin, is the major bioactive component of Epimedium Genus. The present study tested the hypothesis that the neuroprotective effects of Icaritin against 1-Methyl-4-phenylpyridinium ion (MPP(+))-induced toxicity involved activation of the insulin-like growth factor-1 receptor (IGF-1R) signaling pathway in MES23.5 cells. Our results revealed that Icaritin pretreatment attenuated the MPP(+)-induced decrease of cell viability in a dose-dependent fashion. Co-pretreatment with phosphatidylinositol 3-kinase (PI3-K) inhibitor LY294002, mitogen-activated protein kinase (MEK) inhibitor PD98059 or IGF-1 receptor antagonist JB-1 could completely block the protective effects of Icaritin. Moreover, Icaritin pretreatment down-regulated MPP(+)-induced increase of Bax/Bcl-2 ratio transcriptionally and post-transcriptionally. Further study revealed that Icaritin pretreatment could restore the decreased protein expression of Akt and extracellular signal-regulated kinase 1/2 (ERK1/2) induced by MPP(+) and these effects could be completely abolished by LY294002, PD98059 or JB-1. Additionally, Icaritin treatment alone time-dependently enhanced the phosphorylation of Akt and ERK1/2 in MES23.5 cells. The activation of Akt and ERK1/2 by Icaritin could be completely blocked by JB-1, LY294002 or PD98059. Taken together, our data demonstrate that IGF-1 receptor mediated activation of PI3K/Akt and MEK/ERK1/2 signaling pathways are involved in the protective effects of Icaritin against MPP(+)-induced toxicity in MES23.5 cells.
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao 266071, People's Republic of China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China; Department of Special Medicine, Medical College of Qingdao University, Qingdao, People's Republic of China; Department of Physiology, Medical College of Taishan, Taian, People's Republic of China.
authors.forename: Ming-Chun
authors.initials: MC
authors.lastname: Jiang
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao 266071, People's Republic of China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China.
authors.forename: Xiao-Han
authors.initials: XH
authors.lastname: Chen
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao 266071, People's Republic of China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China.
authors.forename: Xia
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao 266071, People's Republic of China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China.
authors.forename: Xue-Jie
authors.initials: XJ
authors.lastname: Zhang
authors.affiliation: Department of Physiology, Shandong Provincial Key Laboratory of Pathogenesis and Prevention of Neurological Disorders and State Key Disciplines, Medical College of Qingdao University, Qingdao 266071, People's Republic of China; Shandong Provincial Collaborative Innovation Center for Neurodegenerative Disorders, People's Republic of China. Electronic address: chenwenfangqd@163.com.
authors.forename: Wen-Fang
authors.initials: WF
authors.lastname: Chen
mesh_terms: D015655:1-Methyl-4-phenylpyridinium / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002867:Chromones / Q000494:pharmacology; D005419:Flavonoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects; D018696:Neuroprotective Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology; D009930:Organic Chemicals / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D002867:Chromones; D005419:Flavonoids; D009025:Morpholines; D018696:Neuroprotective Agents; D009842:Oligopeptides; D009930:Organic Chemicals; C466090:PD 98058; C411572:H 1356; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D017526:Receptor, IGF Type 1; D051057:Proto-Oncogene Proteins c-akt; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D015655:1-Methyl-4-phenylpyridinium; C056599:icariin
keywords: 1-Methyl-4-phenylpyridinium ion; Akt; ERK1/2; Icaritin; Insulin-like growth factor-1 receptor; MES23.5 cells