DOWNREGULATION OF HOMER1B/C IMPROVES NEURONAL SURVIVAL AFTER TRAUMATIC NEURONAL INJURY

被引：27

作者：

Fei, F. ^{[1
]}

Rao, W. ^{[2
]}

Zhang, L. ^{[2
]}

Chen, B. -G. ^{[3
]}

Li, J. ^{[2
]}

Fei, Z. ^{[2
]}

Chen, Z. ^{[1
]}

机构：

[1] Fourth Mil Med Univ, Coll Basic Med, Dept Cell Biol, Xian 710032, Peoples R China

[2] Fourth Mil Med Univ, Xijing Hosp, Dept Neurosurg, Xian 710032, Peoples R China

[3] Tongji Univ, Affiliated Shanghai East Hosp, Cent Lab, Shanghai 200120, Peoples R China

来源：

NEUROSCIENCE | 2014年 / 267卷

基金：

中国国家自然科学基金;

关键词：

neurons; injury; receptors; glutamic acid; Homer1; RNAi; METABOTROPIC GLUTAMATE RECEPTORS; INDUCED OXIDATIVE STRESS; SPINAL DORSAL-HORN; BRAIN-INJURY; GENE-EXPRESSION; INDUCED APOPTOSIS; CORTICAL-NEURONS; LOOSE LIGATION; CELL-DEATH; IN-VITRO;

D O I：

10.1016/j.neuroscience.2014.02.037

中图分类号：

Q189 [神经科学];

学科分类号：

071006 [神经生物学];

摘要：

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-Ca2+ 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. (C) 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

引用

页码：187 / 194

页数：8

共 50 条

[1]

Traumatic Brain Injury Pathophysiology and Treatments: Early, Intermediate, and Late Phases Post-Injury [J].

Algattas, Hanna ;

Huang, Jason H. .

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2014, 15 (01) :309-341

[2]

β-amyloid-induced apoptosis of cerebellar granule cells and cortical neurons:: exacerbation by selective inhibition of group I metabotropic glutamate receptors [J].

Allen, JW ;

Eldadah, BA ;

Faden, AI .

NEUROPHARMACOLOGY, 1999, 38 (08) :1243-1252

[3]

Traumatic subarachnoid hemorrhage: our current understanding and its evolution over the past half century [J].

Armin, Sean S. ;

Colohan, Austin R. T. ;

Zhang, John H. .

NEUROLOGICAL RESEARCH, 2006, 28 (04) :445-452

[4]

Synaptic activity-induced conversion of intronic to exonic sequence in Homer 1 immediate early gene expression [J].

Bottai, D ;

Guzowski, JF ;

Schwarz, MK ;

Kang, SH ;

Xiao, B ;

Lanahan, A ;

Worley, PF ;

Seeburg, PH .

JOURNAL OF NEUROSCIENCE, 2002, 22 (01) :167-175

[5]

Homer: A protein that selectively binds metabotropic glutamate receptors [J].

Brakeman, PR ;

Lanahan, AA ;

OBrien, R ;

Roche, K ;

Barnes, CA ;

Huganir, RL ;

Worley, PF .

NATURE, 1997, 386 (6622) :284-288

[6]

Recent advances in neuroprotection for treating traumatic brain injury [J].

Cernak, Ibolja .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2006, 15 (11) :1371-1381

[7]

Down-regulation of Homer1b/c attenuates glutamate-mediated excitotoxicity through endoplasmic reticulum and mitochondria pathways in rat cortical neurons [J].

Chen, Tao ;

Fei, Fei ;

Jiang, Xiao-fan ;

Zhang, Lei ;

Qu, Yan ;

Huo, Kai ;

Fei, Zhou .

FREE RADICAL BIOLOGY AND MEDICINE, 2012, 52 (01) :208-217

[8]

Homer-1c/Vesl-1L modulates the cell surface targeting of metabotropic glutamate receptor type 1α:: Evidence for an anchoring function [J].

Ciruela, F ;

Soloviev, MM ;

Chan, WY ;

McIlhinney, RAJ .

MOLECULAR AND CELLULAR NEUROSCIENCE, 2000, 15 (01) :36-50

[9]

COPANI A, 1995, J NEUROCHEM, V64, P101

[10]

Novel diketopiperazine enhances motor and cognitive recovery after traumatic brain injury in rats and shows neuroprotection in vitro and in vivo [J].

Faden, AI ;

Knoblach, SM ;

Cernak, I ;

Fan, L ;

Vink, R ;

Araldi, GL ;

Fricke, ST ;

Roth, BL ;

Kozikowski, AP .

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2003, 23 (03) :342-354

← 1 2 3 4 5 →