title: BNIP3 upregulation and EndoG translocation in delayed neuronal death in stroke and in hypoxia.
abstract: OBJECTIVE
  Delayed neuronal death is a hallmark feature of stroke and the primary target of neuroprotective strategies. Caspase-independent apoptosis pathways are suggested as a mechanism for the delayed neuronal injury. Here we test the hypothesis that one of the caspase-independent apoptosis pathways is activated by BNIP3 and mediated by EndoG.
  
  
  METHODS
  We performed immunohistochemistry, Western blotting, cell transfection, subcellular fractionation, and RNA interfering to analyze the expression and localization of BNIP3 and EndoG in degenerating neurons in models of stroke and hypoxia.
  
  
  RESULTS
  BNIP3 was upregulated in brain neurons in a rat model of stroke and in cultured primary neurons exposed to hypoxia. The expressed BNIP3 was localized to mitochondria. Both forced expression of BNIP3 by plasmid transfection and induced expression of BNIP3 by hypoxia in neurons resulted in mitochondrial release and nuclear translocation of EndoG and neuronal cell death. Knockdown of BNIP3 by RNAi inhibited EndoG translocation and protected against hypoxia-induced neuronal death.
  
  
  CONCLUSIONS
  BNIP3 plays a role in delayed neuronal death in hypoxia and stroke and EndoG is a mediator of the BNIP3-activated neuronal death pathway. The results suggest that BNIP3 may be a new target for neuronal rescue strategies.
authors: Department of Human Anatomy and Cell Science, University of Manitoba, Faculty of Medicine, Winnipeg, Manitoba, Canada.
authors: Zhengfeng
authors: Z
authors: Zhang
authors: Xuefen
authors: X
authors: Yang
authors: Surong
authors: S
authors: Zhang
authors: Xiuli
authors: X
authors: Ma
authors: Jiming
authors: J
authors: Kong
mesh_terms: D000818:Animals; D017209:Apoptosis; D004195:Disease Models, Animal; D002534:Hypoxia, Brain / Q000503:physiopathology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D009474:Neurons / Q000502:physiology; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000503:physiopathology*; D014178:Translocation, Genetic / Q000502:physiology; D015854:Up-Regulation
chemical_list: C505650:BNIP3 protein, rat; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011518:Proto-Oncogene Proteins