title: High glucose levels increase the expression of neurotrophic factors             associated with p-p42/p44 MAPK in Schwann cells in vitro.
abstract: Diabetic peripheral neuropathy (DPN) is one of the most common complications of diabetes mellitus. One contributing factor to DPN is altered neurotrophism due to changes in the synthesis and expression of neurotrophins. Schwann cells (SCs) are the myelin-forming cells of the peripheral nervous system that promote nerve regeneration through the expression and secretion of neurotrophic factors (NTFs). Therefore, in this study, using SCs cultured in the presence of high levels of glucose for 24 h, with and without the p42/p44 mitogen-activated protein kinase (MAPK) inhibitor, PD98059, we investigated the effect of high glucose levels on SCs over a short period of time. The cultured cells were evaluated using 3(4,5-dimethylthiazol-2-yl)2,5-diphenyltetrazolium bromide (MTT) assay, Hoechst staining, immunocytochemistry, reverse transcriptase-polymerase chain reaction and western blot analysis. High glucose levels did not promote morphological abnormalities or decrease the viability of SCs. However, high glucose levels enhanced the expression of nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) and induced the activation of p42/p44 MAPK in cultured SCs in a dose-dependent manner. Additionally, the phosphorylation of p42/p44 MAPK may be associated with the expression of NTFs by SCs exposed to high glucose conditions; the excessive activation of p42/p44 MAPK inhibited the expression of NTFs. These observations demonstrate that exposure to high glucose levels lead to acutely elevated levels of NGF and BDNF in SCs over a short period of time, which may be involved in the p42/p44 MAPK pathway.
authors.affiliation: Department of Anatomy, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
authors.forename: Hao
authors.initials: H
authors.lastname: Zhu
authors.forename: Wen-Juan
authors.initials: WJ
authors.lastname: Yu
authors.forename: Yan
authors.initials: Y
authors.lastname: Le
authors.forename: Wen-Jin
authors.initials: WJ
authors.lastname: Wang
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Ting
authors.initials: T
authors.lastname: Gui
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Wang
authors.forename: Wo-Dong
authors.initials: WD
authors.lastname: Shi
authors.forename: Wen-Long
authors.initials: WL
authors.lastname: Ding
authors.forename: Xian-Qun
authors.initials: XQ
authors.lastname: Fan
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D005947:Glucose / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism*; D009414:Nerve Growth Factors / Q000235:genetics* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D014158:Transcription, Genetic / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
chemical_list: D009414:Nerve Growth Factors; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D005947:Glucose