| First Author | Saito A | Year | 2004 |
| Journal | Brain Res Mol Brain Res | Volume | 127 |
| Issue | 1-2 | Pages | 89-95 |
| PubMed ID | 15306124 | Mgi Jnum | J:134596 |
| Mgi Id | MGI:3789394 | Doi | 10.1016/j.molbrainres.2004.05.012 |
| Citation | Saito A, et al. (2004) Modulation of the Omi/HtrA2 signaling pathway after transient focal cerebral ischemia in mouse brains that overexpress SOD1. Brain Res Mol Brain Res 127(1-2):89-95 |
| abstractText | 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. |
