title: Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase.
abstract: BACKGROUND
  Studies have shown that thrombin activation played a central role in cell injuries associated with intracerebral hemorrhage (ICH).
  
  
  OBJECTIVE
  Here, our study investigated the cytotoxicity of thrombin on neurons, and determined the involvement of JNK pathways in thrombin-induced neuronal apoptosis.
  
  
  METHODS
  Primary cultured neurons were treated with different doses of thrombin. Some neurons were given either SP600125 or vehicle. LDH release assay and flow cytometry were used to measure neuronal apoptosis caused by thrombin. The activation of JNK and capases-3 were measured by Western blot.
  
  
  RESULTS
  Our results showed large doses of thrombin that increased the LDH release, the level of cleaved caspase-3 and apoptosis rate of neurons. JNK was activated by thrombin in a time-dependent manner. Administration of SP600125 protects neurons from thrombin-induced apoptosis.
  
  
  CONCLUSIONS
  These data indicate that the activation of JNK is crucial for thrombin-induced neuronal apoptosis, and inhibition of JNK may be a potential therapeutic target for ICH.
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Lei
authors.initials: L
authors.lastname: Bao
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zu
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Qianqian
authors.initials: Q
authors.lastname: He
authors.affiliation: b Department of Neurology , Xuzhou Central Hospital , Xuzhou , Jiangsu , China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhao
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Su
authors.initials: S
authors.lastname: Zhou
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Xinchun
authors.initials: X
authors.lastname: Ye
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Xinxin
authors.initials: X
authors.lastname: Yang
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zan
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Zuohui
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Shi
authors.affiliation: a Department of Neurology , The Affiliated Hospital of Xuzhou Medical College , Xuzhou , Jiangsu , China.
authors.forename: Guiyun
authors.initials: G
authors.lastname: Cui
mesh_terms: D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000196:embryology; D002543:Cerebral Hemorrhage / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D061251:Primary Cell Culture; D051381:Rats; D013917:Thrombin / Q000494:pharmacology* / Q000502:physiology
chemical_list: D000873:Anthracenes; C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; D013917:Thrombin
keywords: Intracerebral hemorrhage; JNK; cytotoxicity