RGD Reference Report - Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation. - Rat Genome Database

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Translocation of apoptosis-inducing factor in vulnerable neurons after transient cerebral ischemia and in neuronal cultures after oxygen-glucose deprivation.

Authors: Cao, G  Clark, RS  Pei, W  Yin, W  Zhang, F  Sun, FY  Graham, SH  Chen, J 
Citation: Cao G, etal., J Cereb Blood Flow Metab. 2003 Oct;23(10):1137-50.
RGD ID: 10047409
Pubmed: PMID:14526224   (View Abstract at PubMed)
DOI: DOI:10.1097/01.WCB.0000087090.01171.E7   (Journal Full-text)

Loss of mitochondrial membrane integrity and the resulting release of apoptogenic factors may play a critical role in mediating hippocampal neurodegeneration after transient global ischemia. In the present study, the authors have cloned and characterized the rat cDNA encoding apoptosis-inducing factor (AIF), an intramitochondrial protein that promotes cell death in a caspase-independent manner upon release into nonmitochondrial compartments. In contrast to the expression patterns of a number of apoptosis-regulatory gene products during brain development, the expression of AIF protein increases gradually with brain maturation and peaks in adulthood. In a rat model of transient global ischemia, AIF was found to translocate from mitochondria to the nucleus in the hippocampal CA1 neurons after ischemia and to manifest a DNA-degrading activity that mimicked the purified AIF protein and was inhibitable by AIF immunodepletion. The temporal profile of AIF translocation after ischemia (24 to 72 hours) coincided with the induction of large-scale DNA fragmentation at the size of 50 kbp, a well-characterized hallmark of AIF-like activity but preceded the formation of internucleosomal DNA fragmentation (72 hours), a DNA degradation associated with the terminal stage of cell death. Further, the nuclear translocation of AIF after ischemia was not blocked by inhibiting caspase-3/-7 activities, but, as shown in neuronal cultures that were challenged with transient oxygen-glucose deprivation, it can be prevented by intracellular delivery of the mitochondria-associated antiapoptotic protein Bcl-xL. The results presented here strongly suggest that mitochondrial release of AIF may be an important factor, in addition to the previously reported cytochrome c and Smac, which could contribute to the selective vulnerability of CA1 neurons to transient global ischemic injury.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
transient cerebral ischemia  ISOAifm1 (Rattus norvegicus)10047409; 10047409mRNA:decreased expression more ...RGD 
transient cerebral ischemia  IEP 10047409mRNA:decreased expression more ...RGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
cellular response to hypoxia  IEP 10047409oxygen-glucose deprivationRGD 

Objects Annotated

Genes (Rattus norvegicus)
Aifm1  (apoptosis inducing factor, mitochondria associated 1)

Genes (Mus musculus)
Aifm1  (apoptosis-inducing factor, mitochondrion-associated 1)

Genes (Homo sapiens)
AIFM1  (apoptosis inducing factor mitochondria associated 1)


Additional Information