title: Marked, sustained expression of a novel 150-kDa oxygen-regulated stress protein, in severely ischemic mouse neurons.
abstract: The 150-kDa oxygen-regulated protein (ORP150) first was described with reference to the central nervous system in cultured astrocytes subjected to dense hypoxia. Subsequently its transcript was found in macrophages within human aortic atherosclerotic plaques, suggesting a role in protecting cells under hypoxic stress. In a mouse model of permanent focal brain ischemia, we aimed to elucidate the constitutive cellular localization in vivo of ORP150 in the central nervous system as well as the sequential alteration in its mRNA and protein expression during this severe ischemic insult. Immunohistochemical study demonstrated that ORP150 protein normally is present predominantly in neurons. The 78-kDa glucose-regulated protein, which is another well-known stress protein retained in the endoplasmic reticulum, also was stained in neurons. During the first 3 h after ischemia, ORP150 antigenicity was markedly enhanced in severely damaged neurons, while the amount of the glucose-regulated protein was decreased. Preceding this change, orp150 mRNA was selectively induced in neurons undergoing postischemic cytoskeletal proteolysis, as early as 1 h after middle cerebral artery occlusion. These results indicated that ORP150 might be regulated by transcriptional level as for many stress proteins, but unlike previously described other stress proteins it was translated in the center of ischemic lesions despite nearly complete energy depletion. In this paper, the biological potentials of ORP150 protein in the setting of brain ischemia in vivo will also be discussed.
authors.affiliation: Fifth Department of Internal Medicine, Hyogo College of Medicine, Nishinomiya 663, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Matsushita
authors.forename: T
authors.initials: T
authors.lastname: Matsuyama
authors.forename: H
authors.initials: H
authors.lastname: Nishimura
authors.forename: T
authors.initials: T
authors.lastname: Takaoka
authors.forename: K
authors.initials: K
authors.lastname: Kuwabara
authors.forename: Y
authors.initials: Y
authors.lastname: Tsukamoto
authors.forename: M
authors.initials: M
authors.lastname: Sugita
authors.forename: S
authors.initials: S
authors.lastname: Ogawa
mesh_terms: D000818:Animals; D001157:Arterial Occlusive Diseases / Q000503:physiopathology; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000503:physiopathology*; D002352:Carrier Proteins / Q000032:analysis / Q000235:genetics; D003599:Cytoskeleton / Q000473:pathology; D000091342:Endoplasmic Reticulum Chaperone BiP; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D017403:In Situ Hybridization; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000032:analysis / Q000235:genetics; D018832:Molecular Chaperones / Q000032:analysis / Q000235:genetics; D009410:Nerve Degeneration / Q000503:physiopathology*; D009474:Neurons / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis; D013997:Time Factors
chemical_list: D002352:Carrier Proteins; D000091342:Endoplasmic Reticulum Chaperone BiP; D018840:HSP70 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D008869:Microtubule-Associated Proteins; D018832:Molecular Chaperones; D011506:Proteins; D012333:RNA, Messenger; C050087:oxygen-regulated proteins