Abstract
150 kDa-oxygen-regulated protein (ORP150) is a novel stress protein localized in the endoplasmic reticulum, which is induced by hypoxia/ischemia. In order to elucidate the role of ORP150 in cerebral infarction following ischemia/reperfusion, transient focal cerebral ischemia was produced in ORP150 transgenic (TG) and knockout (KO) mice in the present study. Mice were subjected to 1 or 3 hours of middle cerebral artery (MCA) occlusion followed by reperfusion for 24 hours. At 24 hours after 1 hour-occlusion, a significant reduction in volume of infarction was found in the cerebral cortex, but not in the striatum, in the ORP150 TG mice as compared to the ORP150 KO mice (P<0.001). However, no significant difference in infarct volume was noted between the two groups at 24 hours after 3 hours-occlusion. Immunohistochemically, loss of microtubule-associated protein 2 (MAP2) staining in the MCA area was observed in the ORP150 KO mice at 24 hours after 1 hour-occlusion. On the other hand, MAP2 staining was still present in the affected cortex of the ORP150 TG mice where a markedly enhanced ORP150 immunoreactivity was demonstrated MAP2 staining disappeared in the affected area at 24 hours after 3 hours-occlusion in both groups, but ORP150 antigenicity was preserved there in the ORP150 TG mice group. At 6 hours after 1 hour-occlusion, when MAP2 staining was evident in the affected cortex, some cortical neurons of the TG mice were Bci-xs/L positive. These findings suggest that ORP150 is a cytoprotective participant against ischemia/reperfusion injury through a reduction of endoplasmic reticulum stress and probably through its inhibitory effects on apoptosis.
