RGD Reference Report - Modulation of the Omi/HtrA2 signaling pathway after transient focal cerebral ischemia in mouse brains that overexpress SOD1. - Rat Genome Database

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Modulation of the Omi/HtrA2 signaling pathway after transient focal cerebral ischemia in mouse brains that overexpress SOD1.

Authors: Saito, A  Hayashi, T  Okuno, S  Nishi, T  Chan, PH 
Citation: Saito A, etal., Brain Res Mol Brain Res. 2004 Aug 23;127(1-2):89-95.
RGD ID: 5688372
Pubmed: PMID:15306124   (View Abstract at PubMed)
DOI: DOI:10.1016/j.molbrainres.2004.05.012   (Journal Full-text)

Omi/HtrA2 is a novel protein that contributes to the regulation of mitochondrial apoptosis after a variety of cell death stimuli in vitro and is thought to negatively control the inhibitor-of-apoptosis protein (IAP) family. However, the Omi/HtrA2 pathway remains unknown in apoptotic neuronal cell death in vivo. To examine the role of the Omi/HtrA2 pathway and its relationship to oxidative stress after reperfusion following cerebral ischemia, we used a transient focal cerebral ischemia (tFCI) model in copper/zinc-superoxide dismutase (SOD1) transgenic mice and wild-type mice. We evaluated the link between the Omi/HtrA2 pathway and the caspase cascade reaction after tFCI by administration of a pan-caspase inhibitor, Z-VAD-FMK. We observed the time-dependent expression of Omi/HtrA2 and its binding to X-chromosome-linked IAP (Omi/XIAP) by immunohistochemistry, Western blotting and coimmunoprecipitation. Translocation of Omi/HtrA2 into the cytosolic space was detected during the early period after tFCI and was not affected by Z-VAD-FMK administration, but it was prevented by SOD1 overexpression. Coimmunoprecipitation revealed that Omi/XIAP transiently increased and that it was prevented by SOD1 overexpression. These results suggest that the Omi/HtrA2 pathway may play an important role in the progress of apoptotic neuronal cell death and that overexpression of SOD1 may attenuate this apoptotic cell death by preventing the Omi/HtrA2 cell signaling pathway.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
middle cerebral artery infarction  ISOHtra2 (Mus musculus)5688372; 5688372protein:increased expression:brain and cytosol (mouse)RGD 
middle cerebral artery infarction  IEP 5688372protein:increased expression:brain and cytosol (mouse)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Htra2  (HtrA serine peptidase 2)

Genes (Mus musculus)
Htra2  (HtrA serine peptidase 2)

Genes (Homo sapiens)
HTRA2  (HtrA serine peptidase 2)


Additional Information