RGD Reference Report - BNIP3 upregulation and EndoG translocation in delayed neuronal death in stroke and in hypoxia. - Rat Genome Database

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BNIP3 upregulation and EndoG translocation in delayed neuronal death in stroke and in hypoxia.

Authors: Zhang, Z  Yang, X  Zhang, S  Ma, X  Kong, J 
Citation: Zhang Z, etal., Stroke. 2007 May;38(5):1606-13. Epub 2007 Mar 22.
RGD ID: 9685412
Pubmed: PMID:17379825   (View Abstract at PubMed)
DOI: DOI:10.1161/STROKEAHA.106.475129   (Journal Full-text)

BACKGROUND AND PURPOSE: 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
BNIP3Humanmiddle cerebral artery infarction  ISOBnip3 (Rattus norvegicus)protein:increased expression:brainRGD 
Bnip3Ratmiddle cerebral artery infarction  IEP protein:increased expression:brainRGD 
Bnip3Mousemiddle cerebral artery infarction  ISOBnip3 (Rattus norvegicus)protein:increased expression:brainRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Bnip3Ratcellular response to hypoxia  IEP  RGD 
EndogRatcellular response to hypoxia  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bnip3  (BCL2 interacting protein 3)
Endog  (endonuclease G)

Genes (Mus musculus)
Bnip3  (BCL2/adenovirus E1B interacting protein 3)

Genes (Homo sapiens)
BNIP3  (BCL2 interacting protein 3)


Additional Information