| Project/Area Number |
12490019
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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 |
広領域
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| Research Institution | The University of Shiga Prefecture (2001)
Kyoto University (2000) |
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Principal Investigator |
SASAKI Ryuzo The Univ. of Shiga Pre. Dept. of life style Studies, Professor, 人間文化学部, 教授 (60077378)
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| Co-Investigator(Kenkyū-buntansha) |
福渡 務 滋賀県立大学, 人間文化学部, 助手 (50295630)
KAMBE Taiho Kyoto Univ. Dept. of Biostudies,, 生命科学研究科, 助手 (90303875)
増田 誠司 京都大学, 生命科学研究科, 助教授 (20260614)
永尾 雅哉 京都大学, 生命科学研究科, 助教授 (10237498)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥13,600,000 (Direct Cost: ¥13,600,000)
Fiscal Year 2001: ¥6,700,000 (Direct Cost: ¥6,700,000)
Fiscal Year 2000: ¥6,900,000 (Direct Cost: ¥6,900,000)
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| Keywords | Erythropoietin / Eryghropoiesis / Neuron death / Ischemia / Brain / Kidney / Gene expression / Hypoxia / 脳虚血 / 低酸素 / 神経保護 / アストログリア / 転写 / mRNA安定化 |
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| Research Abstract |
Erythropoietin (EPO) is a glycoprotein that is produced by the kidney in adults. It has been belived for long time that stimulation of erythropoiesis is a sole physiological function of EPO but we have demonstrated that EPO is produced in brain and protects neurons from ischemic damage. This finding has been supported by a number of papers subsequently publised and recombinant human EPO is going to be examined as a therapeutic of various brain diseases.
Expression of EPO gene is markedly enhanced by hypoxia. Expression of EPO gene in both kidney and brain is hypoxia-inducible but the expression patterns are quite different. When animals are exposed to hypoxia (7 % oxygen), EPO mRNA in both organs increases 40-80-fold at 4 hr after exposure. EPO mRNA is kept at a high level as far as animals are exposed to hypoxia. Although the mechanism remains unknown, this finding implicates the physiological importance that (1) the continuous high level of the kidney EPO mRNA causes erthrocytosis, leading to various vascular disorders and therefore EPO mRNA in the kidney must be decreased despite of hypoxia and that (2) EPO in the brain is required for neuroprotection under hyoxia and therefore a high level continues during hypoxia.
We have shown that EPO is also produced in the uterus where EPO acts as an angiogenic factor for periodical growth of uterine endometrial layer. EPO production in the uterus is also hypoxia-inducible but estrogen is required for hypoxic induction of EPO.
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