| Project/Area Number |
12671106
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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 | Nagoya University |
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Principal Investigator |
HAMADA Yoji (2001) University Hospital, Nagoya University, Research Associate, 医学部・附属病院, 助手 (20293706)
堀田 饒 (2000) 名古屋大学, 医学部, 教授 (60023793)
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| Co-Investigator(Kenkyū-buntansha) |
NAKASHIMA Eitaro University Hospital, Nagoya University, Research Associate, 医学部・附属病院, 助手 (50335030)
NAKAMURA Jiro Graduate School of Medicine, Nagoya University, Associate Professor, 大学院・医学研究科, 助教授 (40283444)
茶谷 貞男 名古屋大学, 医学部, 助手 (30313993)
濱田 洋司 名古屋大学, 医学部, 助手 (20293706)
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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 |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2001: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Diabetic Complications / Retinal MicrovascuLar Pericytes / Apoptosis / Poiyol Pahtway / Protein Kinase C / Oxidentive Stress / Aldose Reductase Inhibitior / プロティンキナーゼC |
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| Research Abstract |
The mechanisms of the glucose-induced apoptosis in retinal pericytes were investigated to evaluate the pathogenesis of diabetic retinopathy. Under the 20 mM glucose condition, intracellular calcium concentrations and caspase-3 activities were significantly increased, and reduced glutathione contents and PKC activities were significantly decreased, compared with those under the 5. 5 mM glucose condition. These abnormalities were all significantly prevented by an aldose reductase inhibitor, SNK-860. Glucose-induced apoptosis was partially but significantly prevented by SNK-860, a calpain inhibitor, or reduced glutathione supplementation, and completely normalized by a caspase-3 inhibitor. These observations suggest that glucose-induced apoptosis in retinal pericytes would be mediated through an aldose reductase sensitive pathway including caicium-calpain cascade, increased oxidative stress and decreased PKC activities, and that caspase-3 would be located furthest down stream of these apoptotic signals.
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