title: Abeta(31-35)-induced neuronal apoptosis is mediated by JNK-dependent extrinsic apoptosis pathway.
abstract: OBJECTIVE
  To investigate whether JNK-caspase-dependent apoptotic pathway is involved in Abeta(31-35)-induced apoptosis of cultured cortical neurons.
  
  
  METHODS
  Cultured cortical neurons were treated with Abeta(31-35) (25 micromol/L) for 4 h, 8 h, 16 h and 24 h, respectively. Caspase activities were measured using a spectrophotometer. Levels of c-Jun phosphorylation (p-c-Jun) and Fas ligand (FasL) expression were assessed by immunocytochemistry method and quantified using Image-pro plus11.0 image processing and analysis software.
  
  
  RESULTS
  Treatment with Abeta(31-35) (25 micromol/L) for 24 h induced significant increases in the activities of caspase-3 and caspase-8 in the cortical neurons. Besides, Abeta(31-35) could time-dependently enhance the expression of p-c-Jun protein. Moreover, SP600125 application (100 nmol/L) could completely abolish Abeta(31-35) neurotoxicity. The increase in FasL expression was detected at 8 h, 16 h and 24 h after Abeta(31-35) treatment, and SP600125 (100 nmol/L) significantly inhibited FasL expression.
  
  
  CONCLUSIONS
  JNK-c-Jun-FasL-caspase-dependent extrinsic apoptotic pathway plays a critical role in mediating Abeta(31-35)-induced apoptosis of cultured neurons.
authors.affiliation: Department of Pathology, Shanxi Medical University, Taiyuan, China.
authors.forename: Ling-Min
authors.initials: LM
authors.lastname: Li
authors.forename: Qing-Hua
authors.initials: QH
authors.lastname: Liu
authors.forename: Jian-Tian
authors.initials: JT
authors.lastname: Qiao
authors.forename: Ce
authors.initials: C
authors.lastname: Zhang
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D053181:Caspase 8 / Q000378:metabolism; D020169:Caspases / Q000378:metabolism*; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology; D053222:Fas Ligand Protein / Q000378:metabolism; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D048031:JNK Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013053:Spectrophotometry; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D000873:Anthracenes; D004791:Enzyme Inhibitors; D053222:Fas Ligand Protein; D010446:Peptide Fragments; C113042:amyloid beta-protein (31-35); C432165:pyrazolanthrone; D048031:JNK Mitogen-Activated Protein Kinases; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D020169:Caspases