title: Oxygen-glucose deprivation preconditioning protects neurons against oxygen-glucose deprivation/reperfusion induced injury via bone morphogenetic protein-7 mediated ERK, p38 and Smad signalling pathways.
abstract: Bone morphogenetic protein (BMP)-7 mediated neuroprotective effect of cerebral ischemic preconditioning (IPC) has been studied in an ischemic animal model, but the underlying cellular mechanisms have not been clearly clarified. In this study, primary cortical neurons and the SH-SY5Y cell line were used to investigate the role of BMP-7 and its downstream signals in the neuroprotective effects of oxygen-glucose deprivation preconditioning (OGDPC). Immunocytochemistry was used to detect the expression of neurofilament in neurons. MTT and lactate dehydrogenase activity assays were used to measure the cytotoxicity. Western blot was used to detect the protein expression of BMP-7 and downstream signals. BMP inhibitor, mitogen-activated protein kinase inhibitors, Smad inhibitor and siRNA of Smad 1 were used to investigate the role of corresponding signalling pathways in the OGDPC. Results showed that OGDPC-induced overexpression of BMP-7 in primary cortical neurons and SH-SY5Y cells. Both of endogenous and exogenous BMP-7 could replicate the neuroprotective effects seen in OGDPC pretreatment. In addition, extracellular regulated protein kinases, p38 and Smad signalling pathway were found to be involved in the neuroprotective effects mediated by OGDPC via BMP-7. This study primarily reveals the cellular mechanisms of the neuroprotection mediated by OGDPC, and provides evidence for better understanding of this intrinsic factor against ischemia.
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Junhong
authors.initials: J
authors.lastname: Guan
authors.affiliation: Department of Neurosurgery, Shenyang Red Cross Hospital, Shenyang, China.
authors.forename: Shaonan
authors.initials: S
authors.lastname: Du
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Lv
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Shengtao
authors.initials: S
authors.lastname: Qu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Fu
authors.affiliation: Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Yuan
mesh_terms: D000818:Animals; D055419:Bone Morphogenetic Protein 7 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005947:Glucose / Q000172:deficiency*; D006801:Humans; D019194:Ischemic Preconditioning; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology*; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D000066829:Neuroprotection / Q000187:drug effects; D010100:Oxygen / Q000378:metabolism*; D051381:Rats; D051785:Smad Proteins / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D055419:Bone Morphogenetic Protein 7; D051785:Smad Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D005947:Glucose; D010100:Oxygen
keywords: BMP-7; MAPK; OGDPC; SH-SY5Y; neurons; smad