RGD Reference Report - Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. - Rat Genome Database

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Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy.

Authors: Hamacher-Brady, A  Brady, NR  Logue, SE  Sayen, MR  Jinno, M  Kirshenbaum, LA  Gottlieb, RA  Gustafsson, AB 
Citation: Hamacher-Brady A, etal., Cell Death Differ. 2007 Jan;14(1):146-57. Epub 2006 Apr 28.
RGD ID: 11561983
Pubmed: PMID:16645637   (View Abstract at PubMed)
DOI: DOI:10.1038/sj.cdd.4401936   (Journal Full-text)

Ischemia and reperfusion (I/R) injury is associated with extensive loss of cardiac myocytes. Bnip3 is a mitochondrial pro-apoptotic Bcl-2 protein which is expressed in the adult myocardium. To investigate if Bnip3 plays a role in I/R injury, we generated a TAT-fusion protein encoding the carboxyl terminal transmembrane deletion mutant of Bnip3 (TAT-Bnip3DeltaTM) which has been shown to act as a dominant negative to block Bnip3-induced cell death. Perfusion with TAT-Bnip3DeltaTM conferred protection against I/R injury, improved cardiac function, and protected mitochondrial integrity. Moreover, Bnip3 induced extensive fragmentation of the mitochondrial network and increased autophagy in HL-1 myocytes. 3D rendering of confocal images revealed fragmented mitochondria inside autophagosomes. Enhancement of autophagy by ATG5 protected against Bnip3-mediated cell death, whereas inhibition of autophagy by ATG5K130R enhanced cell death. These results suggest that Bnip3 contributes to I/R injury which triggers a protective stress response with upregulation of autophagy and removal of damaged mitochondria.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Myocardial Reperfusion Injury treatmentISOBnip3 (Rattus norvegicus)11561983; 11561983 RGD 
Myocardial Reperfusion Injury treatmentIMP 11561983 RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of apoptotic process  IMP 11561983 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Bnip3  (BCL2 interacting protein 3)

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

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


Additional Information