| Project/Area Number |
12671124
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Metabolomics
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| Research Institution | JICHI MEDICAL SCHOOL |
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Principal Investigator |
KUROKI Masatoshi JICHI MEDICAL SCHOOL, ASSOCIATED PROFFESOR, 医学部, 助教授 (90215096)
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| Co-Investigator(Kenkyū-buntansha) |
YASU Takanori JICHI MEDICAL SCHOOL, ASSISTANT PROFFESOR, 医学部, 助手 (40265278)
UEBA Hiroto JICHI MEDICAL SCHOOL, ASSISTANT PROFFESOR, 医学部, 助手 (80316546)
KAWAKAMI Masaobu JICHI MEDICAL SCHOOL, PROFFESOR, 医学部, 教授 (40161286)
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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 |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,300,000 (Direct Cost: ¥2,300,000)
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| Keywords | HYPOXIA / VEGF / NADPH OXIDASE / REACTIVE OXYGEN SPECIES / NITRIC OXIDE / NO SYNTHASE / MITCHONDRIAL ELECTRON TRANSPORT / NADPHオキシダーゼ / 一酸化窒素 / HNF-4 / ATP / K-ATPチャンネル |
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| Research Abstract |
Oxygen sensing system in the body induces the production of various molecules like erythropoietin and vascular endothelial growth factor (VEGF) to avoid any mismatch between oxygen demand and oxygen supply in the case of anemia or ischemic vascular disease. On the other hand, the neovascularization induced by ischemia (hypoxia) worsens the process of a cancer or a diabetic retinopathy. However, the sensor and the intracellular signaling system of the hypoxia (the concentration of oxygen) remain unclear. Therefore, we examined the mechanisms of the VEGF gene expression induced by hypoxia in this study.
Our study presented evidence that the hypoxia increases the intracellular generation of reactive oxygen species (ROS), which works the second messenger for the expression of VEGF gene. Furthermore, it became clear that nitric oxide (NO) also works as the second messenger, which negatively stimulates the hypoxia-induced expression of VEGF. Thus, the generating systems of ROS and NO may simultaneously affect as the oxygen sensor of the cells. In this study, we found that NADPH oxidase, one of the ROS generating structures in the cells, is not the sensor of hypoxia. Our results revealed that the hypoxiainduced VEGF gene expression is regulated by ROS generated from mitochodrial electron transport or arachidonic acid metabolic pathway. And our results also revealed that the intracellular ATP content possibly works as the sensor of the hypoxia and the ATP-regulated K (K-ATP) channel may be one of the sensing systems of hypoxia.
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