2001 Fiscal Year Final Research Report Summary
Hypoxia-Mediated induction of heme oxygenase type I and carbon monoxide release from astrocytes protects nearby cerebellar neurons from hypoxia-mediated apoptosis.
| Project/Area Number |
10308034
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Nerve anatomy/Neuropathology
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| Research Institution | Osaka University |
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Principal Investigator |
TOHYAMA Masaya Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 教授 (40028593)
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| Co-Investigator(Kenkyū-buntansha) |
OGAWA Satoshi Kanazawa University School of Medicine, Professor, 医学部, 教授 (90283746)
YAMASHITA Toshihide Osaka University Graduate School of Medicine, Associate Professor, 医学系研究科, 助教授 (10301269)
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| Project Period (FY) |
1998 – 2001
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| Keywords | ORP150 / Neuronal cell death / Ischemia / hypoxia |
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| Research Abstract |
To study a putative paracellular protective mechanism of astrosytes for neurons, immunohistochemical analysis was performed in ischemic rat brain, which colocalized with the expression of heme oxygase1 (HO-1) in astrocytes surrounding dying, TUNEL positive neurons. As an in vitro paradigm for ischemia, cultured astrocytes were exposed to normobaric hypoxia(pO2〜10 torr), which triggered〜120-fold increase in the expression of a 33 kDa stress protein, identiried as HO-1. Induction of H0-1 message was observed within 4 hrs of hypoxia and peaked at 12 hours, accompanied by an accelerated transcription of HO-1 message. Consistent with the induction of HO-1 a platelet bioassay revealed production of carbon monoxide by reoxygenated astrocytes. The presence of CO in the medium decelerated the hypoxiamediated apoptotic type of cell death in cultreud cerebellar neurons via lowering the activity of CPP32, a key enzyme regulating apoptotic cell death. This protection against apoptosis was likely mediated by CO-mediated increases in intracellular cGMP levels, and addition of cGMP analogue to hypoxic neuronal cultures suppressed CPP32 activity and promoted neuronal survival. These data describe a potentially important paracellular pathway through which astrocytes may rescue neaby neurons from ischemic death.
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Research Products
(9 results)
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[Publications] Tamatani, M., Matsuyama, T., Yamaguchi, A., Mitsuda, N., Tsukamoto, Y., Taniguchi, M., Che, Y.H., Ozawa, K., Hori, O., Nishimura, H., Yamashita, A., Okabe, M., Yanagi, H., Stern, D.M., Ogawa, S., Tohyama, M.: "ORP150 protects against hypoxia/ischemia-induced neuronal death"Nature. Medicine. 7. 317-323 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Matsuzaki, H., Tamatani, M., Yamaguchi, A., Namikawa, K., Kiyama, H., Vitek, M.P., Mitsuda, N., Tohyama, M.: "Vascular endothelial growth factor rescues hippocampal neurons from glutamate-induced toxicity : signal transduction cascades"Faseb Journal,. 12. 1218-1220 (2001)
Description
「研究成果報告書概要(和文)」より
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[Publications] Tamatani M, Matsuyama T, Yamaguchi A, Mitsuda N, Tsukamoto Y, Taniguchi M, Che YH, Ozawa K, Hori O, Nishimura H, Yamashita A, Okabe M, Yanagi H, Stern DM, Ogawa S, <Tohyama M>__________-.: "ORP150 protects against hypoxia/ischemia-induced neuronal death"Nat. Med.. 7. 317-323 (2001)
Description
「研究成果報告書概要(欧文)」より
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[Publications] Sato N., Hori, O., Yamaguchi, A., Lambert, J. C., Chartier-Harlin, M. C., Robinson, P. A., Delacourte, A., Schmidt, A. M., Furuyama, T., Imaizumi, K., <Tohyama. M>__________-. and Takagi, T.: "A novel presenilin-2 splice varian in human Alzheimer's disease brain tissue"J. Neurohem. 72. 2498-505 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Ozawa K, Kuwabara K, Tamatani M, Takatsuji K, Tsukamoto Y, Kaneda S, Yanagi H, Stern DM, Eguchi Y, Tsujimoto Y, Ogawa S, <Tohyama M>_________-.: "150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death"J. Biol. Chem. 274. 6397-6404 (1999)
Description
「研究成果報告書概要(欧文)」より
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