title: Dynamic change of SGK expression and its role in neuron apoptosis after traumatic brain injury.
abstract: OBJECTIVE
  Activation of specific signaling pathways in response to mechanical trauma causes delayed neuronal apoptosis; GSK-3β/β-catenin signaling plays a critical role in the apoptosis of neurons in CNS diseases, SGK was discovered as a regulator of GSK-3β/β-catenin pathway, The goal of this study was to determine if the mechanism of cell death or survival mediated by the SGK/GSK-3β/β-catenin pathway is involved in a rat model of TBI.
  
  
  METHODS
  Here, an acute traumatic brain injury model was applied to investigate the expression change and possible roles of SGK, Expression of SGK, and total-GSK-3β, phospho-GSK3β on ser-9, beta-catenin, and caspase-3 were examined by immunohistochemistry and Western blot analysis. Double immunofluorescent staining was used to observe the SGK localizations. Si-RNA was performed to identify whether SGK regulates neuron apoptosis via GSK-3β/β-catenin pathway, ultimately inhibit caspase-3 activation.
  
  
  RESULTS
  Temporally, SGK expression showed an increase pattern after TBI and reached a peak at day 3. Spatially, SGK was widely expressed in the neuron, rarely in astrocytes and oligodendrocytes; in addition, the expression patterns of active caspase-3 and phospho-GSK3β were parallel with that of SGK, at the same time, the expression of β-catenin shows similarity with SGK. In vitro, to further investigate the function of SGK, a neuronal cell line PC12 was employed to establish an apoptosis model. We analyzed the association of SGK with apoptosis on PC12 cells by western blot, immunofluorescent labeling and siRNA.
  
  
  CONCLUSIONS
  the results implied that SGK plays an important role in neuron apoptosis via the regulation of GSK3β/β-catenin signaling pathway; ultimately inhibit caspase-3 activation. Taken together, we inferred traumatic brain injury induced an upregulation of SGK in the central nervous system, which show a protective role in neuron apoptosis.
authors.affiliation: Department of Neurology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, People's Republic of China.
authors.forename: Xinmin
authors.initials: X
authors.lastname: Wu
authors.forename: Hui
authors.initials: H
authors.lastname: Mao
authors.forename: Jiao
authors.initials: J
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Xu
authors.forename: Jianhua
authors.initials: J
authors.lastname: Cao
authors.forename: Xingxing
authors.initials: X
authors.lastname: Gu
authors.forename: Gang
authors.initials: G
authors.lastname: Cui
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D001930:Brain Injuries / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D015971:Gene Expression Regulation, Enzymologic; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D016716:PC12 Cells; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D013997:Time Factors; D014162:Transfection; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism; D000099184:Serum-Glucocorticoid Regulated Kinases
chemical_list: D053148:Caspase 3; D038362:Glycogen Synthase Kinase 3; D000071679:Glycogen Synthase Kinase 3 beta; D017874:Immediate-Early Proteins; D017346:Protein Serine-Threonine Kinases; D012333:RNA, Messenger; D051176:beta Catenin; D000099184:Serum-Glucocorticoid Regulated Kinases; C495268:Ctnnb1 protein, rat; C000605508:Gsk3b protein, rat; C505410:Casp3 protein, rat
keywords: GSK3β/β-catenin signaling pathway; SGK; neuron apoptosis; traumatic brain injury (TBI)