| Project/Area Number |
09306025
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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 |
Applied molecular and cellular biology
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| Research Institution | KYOTO UNIVERSITY |
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Principal Investigator |
SASAKI Ryuzo Kyoto University, Graduate School of Biostudies, Professor, 生命科学研究科, 教授 (60077378)
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| Co-Investigator(Kenkyū-buntansha) |
YASUDA Yoshiko Kinki University, Medical School, Professor, 医学部, 教授 (10025629)
MASUDA Seiji Kyoto University, Graduate School of Biostudies, Professor, 生命科学研究科, 助教授 (20260614)
NAGAO Masaya Kyoto University, Graduate School of Biostudies, Professor, 生命科学研究科, 助教授 (10237498)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥34,200,000 (Direct Cost: ¥34,200,000)
Fiscal Year 1999: ¥8,300,000 (Direct Cost: ¥8,300,000)
Fiscal Year 1998: ¥9,300,000 (Direct Cost: ¥9,300,000)
Fiscal Year 1997: ¥16,600,000 (Direct Cost: ¥16,600,000)
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| Keywords | erithropoietin / brain / uterus / oriduct / neuron death / angiogenesis / cell technology / oxygen / 腎臓 / エストロゲン / 神経細胞 / 虚血 / 神経栄養因子 / 低酸素 / 血管新生 / 中枢神経系 / 虚血性神経細胞因子 |
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| Research Abstract |
Erythropoietin (EPO) is a glycoprotein produced by the kidney in an oxygen-dependent manner; hypoxia activates EPO production dramatically. EPO has been believed to act exclusively on erythroid precursor cells, stimulating red blood cell formation. However, we found that EPO is produced in other sites where EPO production is regulated in tissue-specific manner and that EPO manifests unexpected new physiological functions in these sites as summarized below.
1.EPO is produced in the central nervous system. The brain EPO acts on EPO receptor expressed in neurons, preventing the neuronal damage from ischemic insult. EPO production is hypoxia-inducible as it is in the kidney.
2.EPO is also produced in female reproductive organs (uterus and oviduct). The uterine EPO stimulates uterine angiogenesis that occurs periodically in the estrous cycle but the oviductal function of EPO remains to be studied. Estrogen is a major inducer of EPO in both organs, although oxygen also contributes the regulation of EPO production. Interestingly, the hypoxic activation of the EPO gene expression in the uterus requires the presence of estrogen.
3.Oxygen supply is one of the major problems in the production of useful proteins by cultured animal cells and therefore it is of importance to devise a system by which a high productivity of recombinant proteins can be maintained or enhanced under low oxygen concentrations. A number of hypoxia-inducible genes have been found in animal cells. A consensus sequence (HRE=hypoxia-response enhancer) responsible for the hypoxic activation exists in these genes. We provided a novel system which guarantees a high productivity even under low oxygen concentrations by the use of the biological strategy based on the hypoxic induction of gene transcription.
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