title: Downregulation of Homer1b/c improves neuronal survival after traumatic neuronal injury.
abstract: Homer protein, a member of the post-synaptic density protein family, plays an important role in the neuronal synaptic activity and is extensively involved in neurological disorders. The present study investigates the role of Homer1b/c in modulating neuronal survival by using an in vitro traumatic neuronal injury model, which was achieved by using a punch device that consisted of 28 stainless steel blades joined together and produced 28 parallel cuts. Downregulation of Homer1b/c by specific siRNA significantly (p<0.05) alleviated the cytoplasmic calcium levels and neuron lactate dehydrogenase release, and ultimately decreased the apoptotic rate after traumatic neuronal injury compared with non-targeting siRNA control treatment in cultured rat cortical neurons. Moreover, the expression of metabotropic glutamate receptor 1a (mGluR1a) was significantly (p<0.05) reduced in the Homer1b/c siRNA-transfected neurons after injury. Therefore, Homer1b/c not only modulated the mGluR1a-inositol 1,4,5-triphosphate receptors-Ca(2+) signal transduction pathway, but also regulated the expression of mGluR1a in mechanical neuronal injury. These findings indicate that the suppression of Homer1b/c expression potentially protects neurons from glutamate excitotoxicity after injury and might be an effective intervention target in traumatic brain injury.
authors.affiliation: Department of Cell Biology, College of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: F
authors.initials: F
authors.lastname: Fei
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: W
authors.initials: W
authors.lastname: Rao
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Central Laboratory, Tongji University Affiliated Shanghai East Hospital, Shanghai 200120, PR China.
authors.forename: B-G
authors.initials: BG
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China.
authors.forename: J
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: feizhou@fmmu.edu.cn.
authors.forename: Z
authors.initials: Z
authors.lastname: Fei
authors.affiliation: Department of Cell Biology, College of Basic Medicine, Fourth Military Medical University, Xi'an 710032, PR China. Electronic address: znchen@fmmu.edu.cn.
authors.forename: Z
authors.initials: Z
authors.lastname: Chen
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D002470:Cell Survival / Q000502:physiology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D015536:Down-Regulation / Q000502:physiology*; D004622:Embryo, Mammalian; D000072233:Homer Scaffolding Proteins; D020287:In Situ Nick-End Labeling; D006899:Mixed Function Oxygenases / Q000378:metabolism; D009474:Neurons / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D014162:Transfection
chemical_list: D002352:Carrier Proteins; D000072233:Homer Scaffolding Proteins; C000606624:Homer1 protein, rat; D034741:RNA, Small Interfering; D018094:Receptors, Metabotropic Glutamate; C102718:metabotropic glutamate receptor 3; C104077:metabotropic glutamate receptor type 1; D006899:Mixed Function Oxygenases; C021497:lactate 2-monooxygenase; D002118:Calcium
keywords: Homer1; RNAi; glutamic acid; injury; neurons; receptors