| Project/Area Number |
18390204
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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-ichi The University of Tokyo, Graduate School of Medicine, Professor (40166947)
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| Co-Investigator(Kenkyū-buntansha) |
UEMURA Koichi Tokyo Medical and Dental University, Public health Graduate School, Professor (30244586)
SHINTANI Kaori University of Tokyo, Graduate School of Medicine, Research Associate (50345047)
MORIMOTO Keiko Nara Women's University, Faculty of Life&Environment, Professor (30220081)
KIMURA Hiroko Juntendo University, School of Medicine, Associate professor (00053299)
TAKAHASHI Kou University of Tokyo, Graduate School of Medicine, Research Assistant (90363803)
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| Project Period (FY) |
2006 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| Budget Amount *help |
¥15,410,000 (Direct Cost: ¥15,200,000、Indirect Cost: ¥210,000)
Fiscal Year 2007: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2006: ¥14,500,000 (Direct Cost: ¥14,500,000)
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| Keywords | Life-style diseases / Oxidative stress / 4-Hydroxynonenal (HNE) / Nitorotyrosine (NT) / Psychological stress / hypertension / Myocardial ischemia / Connexin 43 / 4-Hydroxynonenal / Nitorotyrosine(NT) / 循環器・高血圧 / ストレス / シグナル伝達 / 糖尿病 / 過酸化脂質 |
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| Research Abstract |
1) Contribution of 4-Hydroxynonenal (HNE) and Nitorotyrosine (NT) to pathogenesis of life-style diseases Post-menopausal women showed greater and sustained increase in blood pressure and serum HNE than young women after a psychological stress Color Word Test. Similarly, ovariectomized (OVX) rat showed greater increase in serum NT and blood pressure (BP). Additionally, in spontaneously hypertensive rat (SHR), treadmill exercise suppressed the onset of hypertension and increases in NT and HNE in serum and aorta. These results demonstrated that oxidative stress is involved in the pathogenesis of postmenopausal cardiovascular diseases and hypertension. In OVX rat, visceral fat and insulin resistance were increased, whereas the endothelial nitric oxide synthase (eNOS) expression was decreased in the mesentery. These results suggest that OVX rat provide a model of metabolic syndrome.
2) Contribution of HNE to the pathogenesis of inflammation After LPS administration, the serum HNE in the rat increased transiently from the superoxide derived from monocyte NADPH oxidase. In the intestinal mucosa, IgA was secreted post-LPS from plasma cells after HNE modification and polymerization. Additionally, CYP and NADPH oxidase generate superoxide and HNE in the endoplasmic reticulum, thereby contributing to HNE modification and limited proteolysis of GRP78.
3) Connexin 43 (Cx43) up-regulates in cardiomyocytes and contributes to injury and death in ischemia-reperfusion. Coronary artery occlusion in the rat increases Cx43 expression and gap junction interecellular communication, thereby contributing to the propagation of contraction band necrosis and infarct development. In the cultured cardiomyocytes, the transient Cx43 up-regulation during ischemia induces Ca^<2+> influx via hemichannel and cell death.
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