title: Suppression of Glutamate Carboxypeptidase II Ameliorates Neuronal Apoptosis from Ischemic Brain Injury.
abstract: BACKGROUND
  Ischemia stroke is a destructive cerebrovascular disease and a major cause of death and lifelong neurological disability. N-Acetyl-l-aspartyl-l-glutamate (NAAG) is a neurotransmitter in the mammalian brain and involves a variety of physiological and pathological functions including ischemia brain injury. Full understanding of the functions of NAAG peptidase (GCPII) in the pathogenesis of ischemia brain injury is extremely valuable for effective therapies to ischemia stroke.
  
  
  METHODS
  The expressions of GCPII and NAAG agonist metabotropic glutamate receptor (mGluR3) and TGFb1 were examined by real-time polymerase chain reaction and western blot. Moreover, GCPII knockdown cells were constructed using lentivirus-mediated transfection. Function and molecular mechanisms of GCPII knockdown on apoptosis induced from hypoxic-ischemic-induced injury in neuronal cells were analyzed.
  
  
  RESULTS
  In this study, we found that the expressions of GCPII and mGluR3 were upregulated in CoCl2-induced hypoxia environment in neuronal cells. Moreover, knockdown of GCPII in neuronal cells ameliorated apoptosis from hypoxic-ischemic-induced injury through suppressing expressions of caspase 3 and caspase 9.
  
  
  CONCLUSIONS
  Our results highlighted the roles of GCPII in the ischemia brain injury, and might provide an important target in therapeutic implications.
authors.affiliation: Department of Neurosurgery, Yuyao People's Hospital of Zhejiang Province, Yuyao City, Zhejiang, China. Electronic address: zhang951154@sina.com.
authors.forename: Weiqiao
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Yuyao People's Hospital of Zhejiang Province, Yuyao City, Zhejiang, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, Yuyao People's Hospital of Zhejiang Province, Yuyao City, Zhejiang, China.
authors.forename: Liping
authors.initials: L
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, Shanghai, China.
authors.forename: Yongming
authors.initials: Y
authors.lastname: Qiu
authors.affiliation: Department of Neurosurgery, Renji Hospital, School of Medicine, Shanghai Jiao-tong University, Shanghai, China.
authors.forename: Yingying
authors.initials: Y
authors.lastname: Lin
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000201:enzymology* / Q000473:pathology; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053453:Caspase 9 / Q000235:genetics / Q000378:metabolism; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D060833:Cellular Microenvironment; D004195:Disease Models, Animal; D015536:Down-Regulation; D043425:Glutamate Carboxypeptidase II / Q000235:genetics / Q000378:metabolism*; D020244:Infarction, Middle Cerebral Artery / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009474:Neurons / Q000201:enzymology* / Q000473:pathology; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014162:Transfection; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D018094:Receptors, Metabotropic Glutamate; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C102718:metabotropic glutamate receptor 3; D043425:Glutamate Carboxypeptidase II; C505410:Casp3 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053453:Caspase 9
keywords: Ischemia stoke; NAAG peptidase; hypoxia; metabotropic glutamate receptor; neuronal apoptosis