title: Apoptotic and necrotic death mechanisms are concomitantly activated in the same cell after cerebral ischemia.
abstract: OBJECTIVE
  Both necrotic and apoptotic cell death mechanisms are activated after cerebral ischemia. However, whether they are concomitantly active in the same cell or in discrete cell populations is not known.
  
  
  METHODS
  We investigated activation of both pathways at the cellular level in mice brains subjected to transient or permanent focal ischemia.
  
  
  RESULTS
  Four hours after ischemia, diffuse cathepsin-B spillage into cytoplasm, suggesting lysosomal leakage, was observed within neurons immunoreactive for the active form of caspase-3 (p20). Ischemic neurons with a leaky plasma membrane (positive for propidium iodide) were colabeled with caspase-cleaved actin fragment and exhibited TUNEL-positive nuclei having apoptotic morphology. At 72 hours, up to 27% of cells with caspase activity displayed morphological features suggestive of secondary necrosis.
  
  
  CONCLUSIONS
  These data, demonstrating an early and concurrent increase in caspase-3 and cathepsin-B activities followed by appearance of caspase-cleavage products, DNA fragmentation, and membrane disintegration, suggest that subroutines of necrotic and apoptotic cell death are concomitantly activated in ischemic neurons and that the dominant cell death phenotype is determined by the relative speed of each process.
authors.affiliation: Department of Neurology, Faculty of Medicine, and the Institute of Neurological Sciences and Psychiatry, Hacettepe University, Ankara, Turkey.
authors.forename: Isin
authors.initials: I
authors.lastname: Unal-Cevik
authors.forename: Munire
authors.initials: M
authors.lastname: Kilinç
authors.forename: Alp
authors.initials: A
authors.lastname: Can
authors.forename: Yasemin
authors.initials: Y
authors.lastname: Gürsoy-Ozdemir
authors.forename: Turgay
authors.initials: T
authors.lastname: Dalkara
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002401:Cathepsin B / Q000378:metabolism; D002463:Cell Membrane Permeability; D002467:Cell Nucleus / Q000648:ultrastructure; D053938:DNA Fragmentation; D004789:Enzyme Activation; D020287:In Situ Nick-End Labeling; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology*; D008247:Lysosomes / Q000201:enzymology; D051379:Mice; D009336:Necrosis; D009474:Neurons / Q000473:pathology*; D013997:Time Factors
chemical_list: D000199:Actins; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D002401:Cathepsin B