ORP150 ameliorates ischemia/reperfusion injury from middle cerebral artery occlusion in mouse brain.
The 150-kDa oxygen-regulated protein (ORP150), a novel stress protein localized to the endoplasmic reticulum (ER), is induced by hypoxia/ischemia. To determine the role of ORP150 in cerebral infarction following ischemia/reperfusion, ORP150 transgenic (TG) and knockout (KO) mice were subjected to 1 or 3 h of middle cerebral artery (MCA) occlusion followed by reperfusion for 24 h. At 24 h after 1 h of occlusion, significantly less infarct volume was evident in cerebral cortex, but not in striatum, in ORP150TG than ORP150KO mice (P<0.001). Infarct volume did not differ significantly between these groups at 24 h after 3 h of occlusion. Immunohistochemical reactivity for microtubule-associated protein (MAP)2 in the MCA territory was lost in ORP150KO mice at 24 h after 1 h of occlusion. In contrast, MAP2 staining still was present in the affected cortex of ORP150TG mice, where markedly enhanced ORP150 immunoreactivity was demonstrated. MAP2 staining had disappeared from the affected area at 24 h after 3 h of occlusion in both groups, but astrocytic ORP150 reactivity was preserved in the ORP150TG group. At 6 h after 1-h occlusion, when MAP2 staining was evident in the affected cortex, some cortical neurons of the TG mice were reactive for Bcl-xS/L. Thus, ORP150 may be cytoprotective against ischemia/reperfusion injury via reduction of ER stress and probably also inhibition of apoptosis.
Kitano
H
H
Department of Internal Medicine, Division of Neurology and Stroke Care Unit, Hyogo College of Medicine, 1-1 Mukogawachou, Nishinomiya City, Hyogo, 663-8501, Japan. tomohiro@hyo-med.ac.jp
Nishimura
H
H
Tachibana
H
H
Yoshikawa
H
H
Matsuyama
T
T
D000818:Animals; D002545:Brain Ischemia / Q000150:complications / Q000503:physiopathology; D016923:Cell Death / Q000502:physiology; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000503:physiopathology; D002544:Cerebral Infarction / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D003342:Corpus Striatum / Q000098:blood supply / Q000166:cytology / Q000503:physiopathology; D019610:Cytoprotection / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018840:HSP70 Heat-Shock Proteins; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000503:physiopathology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009474:Neurons / Q000473:pathology; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D015427:Reperfusion Injury / Q000517:prevention & control*; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D011506:Proteins; C050087:oxygen-regulated proteins