| Project/Area Number |
09470241
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Kobe University |
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Principal Investigator |
NAKAMURA Hajime Kobe University School of Medicine, Professor, 医学部, 教授 (40030978)
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| Co-Investigator(Kenkyū-buntansha) |
SOMA Osamu Kobe University School of Medicine, Assistant Professor, 医学部・附属病院, 助手 (70283893)
TSUNEISHI Syuichi Kobe University School of Medicine, Assistant Professor, 医学部・附属病院, 助手 (10271040)
YONETANI Masahiko Kobe University School of Medicine, Assistant Professor, 医学部, 助手 (60221678)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥12,200,000 (Direct Cost: ¥12,200,000)
Fiscal Year 1998: ¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 1997: ¥8,600,000 (Direct Cost: ¥8,600,000)
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| Keywords | hypoxia / ischemia / brain damage / neonate / heme oxygenase-1 |
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| Research Abstract |
Heme oxygenase-1 (HO-1) is an inducible enzyme in heme catabolism that cleaves heme to form biliverdin, carbon monoxide and iron. Although HO-1 is only expressed at a basal level in the normal rodent brain, the expression of HO-1 is strongly activated response to various stumuli. We investigated the quantitative changes in HO-1 mRNA and protein levels in 7-day-old rat model of hypoxic-ischemic (HI) brain damage. The amount of HO-1 protein was the highest on the ligated side of the hippocampus, and it increased to a maximum at 12 hrs following HI insult. The level of HO-1 mRNA had already increased by the end of HI, reached a maximum at 3 hrs following HI insult and then decreased. The time course of the HO-1 protein induction was essentially consistent with that of HO-1 mRNA.In the newborn hypoxic-ischemic rat model, the expression of HO-1 is induced at an earlier stage compared to that in the adult ischemic rat model. 158
To clarify the biological effects of HO-1 against developing brain cells, we analyzed the influence of HO-1 induced by heat shock treatment (42 degree, 30 min) on glial differentiation. Rat glioma cell line, C6, can express both proteolipid protein (PLP) with retinoic acid treatment and glial fibrillary acidic protein (GFAP) with dbcAMP treatment. Heat shock treatment suppressed PLP expression and enhanced GFAP expression in C6 cells. Heat shock proteins, including HO-1, may interfere the glial differentiation resulting in perinatal white matter lesion.
Defense mechanism of HO-1 against oxidative stress begins to work at the early stages of HI insult in the vulnerable perinatal brain and may contribute to protect against brain damage resulting from a combination of hypoxia and ischemia during the perinatal period. However, induced heat shock proteins may affect the glial differentiation leading to white matter lesion.
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