Molecular pathological study on vascular lesions due to ischemic heart diseases and related diseases
| Project/Area Number |
16390191
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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 |
Legal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
YOSHIDA Ken-ich The University of Tokyo, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (40166947)
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| Co-Investigator(Kenkyū-buntansha) |
UMEMURA Kouich The University of Tokyo, Graduate School of Medicine, Lector, 大学院・医学系研究科, 講師 (30244586)
SHINTANI Kaori The University of Tokyo, Graduate School of Medicine, Assistant, 大学院・医学系研究科, 助手 (50345047)
KIMURA Hiroko Juntendo University, School of Medicine, lecturer, 医学部, 講師 (00053299)
池谷 博 東京大学, 大学院・医学系研究科, 助手 (30292874)
森本 恵子 奈良女子大学, 生活環境学部, 教授 (30220081)
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| Project Period (FY) |
2004 – 2005
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| Project Status |
Completed (Fiscal Year 2005)
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| Budget Amount *help |
¥12,700,000 (Direct Cost: ¥12,700,000)
Fiscal Year 2005: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 2004: ¥10,900,000 (Direct Cost: ¥10,900,000)
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| Keywords | Ishemia reperfusion / Nitric oxide / Reactive oxygen species / Blood plow / Lipid peroxidation / Myocardial cell death / Metabolic syndrome / Inflammation / 虚血性心疾患 / アポトーシス / コネクシン / 不整脈 |
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| Research Abstract |
After short (<30 min) and long (>45 min) time of ischemia conferred by coronary artery occlusion of the rats, reperfusion caused dilatation and constriction of arterioles, respectively. The vascular diameter was correlated with phosphorylation of Akt and serine 1177 residue of eNOS. Reactive oxygen species (ROS) generation and PKC activation contribute to the vasoconstriction through inhibition of eNOS phosphorylation. In the blood of Lipopolysaccaride-injected rat, monocyte NADPH generate ROS, thereby promoting HNE production, as detected by the highly sensitive immunoassay that we have developed.
We have developed a time-resolved fluoroimmunoassay for a lipid peroxide 4-hydroxynonenal (HNE), which is 100-fold more sensitive than conventional ELISA. By this assay, we found that a low dose bacterial lipo-polysaccharide (LPS) increased serum HNE, with a peak at 20 min. LPS increased HNE in vitro in the monocyte-enriched plasma, which was inhibited by a specific NADPH oxidase inhibitor. These data suggest that monocyte NADPH oxidase is involved in the lipid peroxidation (HNE formation) in the LPS-challenged rat.
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Report
(3 results)
Research Products
(25 results)
