RGD Reference Report - Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain. - Rat Genome Database

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Involvement of apoptosis-inducing factor in neuronal death after hypoxia-ischemia in the neonatal rat brain.

Authors: Zhu, C  Qiu, L  Wang, X  Hallin, U  Cande, C  Kroemer, G  Hagberg, H  Blomgren, K 
Citation: Zhu C, etal., J Neurochem. 2003 Jul;86(2):306-17.
RGD ID: 10053564
Pubmed: PMID:12871572   (View Abstract at PubMed)

Apoptosis-inducing factor (AIF) triggers apoptosis in a caspase-independent manner. Here we report for the first time involvement of AIF in neuronal death induced by cerebral ischemia. Unilateral cerebral hypoxia-ischemia (HI) was induced in 7-day-old rats by ligation of the left carotid artery and hypoxia (7.7% O2) for 55 min. AIF release from mitochondria and AIF translocation to nuclei was detected immediately after HI, and only in damaged areas, as judged by the concurrent loss of MAP-2. AIF release was detected earlier than that of cytochrome c. Cells with AIF-positive nuclei displayed nuclear condensation and signs of DNA damage. The number of AIF-positive nuclei showed a positive correlation with the infarct volume 72 h post-HI, and this was not changed by treating the animals with boc-Asp-fmk (BAF), a multicaspase inhibitor. BAF treatment reduced the activity of caspase-3, -2 and -9 (78, 73 and 33%, respectively), and prevented caspase-dependent fodrin cleavage in vivo, but did not affect AIF release from mitochondria or the frequency of positive nuclear AIF or DNA damage 72 h post-HI, indicating that these processes occurred in a caspase-independent fashion. In summary, AIF-mediated cell death may be an important mechanism of HI-induced neuronal loss in the immature brain.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Brain Hypoxia-Ischemia  ISOAifm1 (Rattus norvegicus)10053564; 10053564protein:increased expression:nucleus:RGD 
Brain Hypoxia-Ischemia  IEP 10053564protein:increased expression:nucleus:RGD 

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