Therapeutic potency of antioxidative peptide in metabolic syndrome
| Project/Area Number |
16590660
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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 |
Circulatory organs internal medicine
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| Research Institution | The University of Tokyo |
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Principal Investigator |
SHIMOSAWA Tatsuo The University of Tokyo, Faculty of Medicine, Lecturer, 医学部附属病院, 講師 (90231365)
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| Co-Investigator(Kenkyū-buntansha) |
TAKAHASHI Katsutoshi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (00292863)
ISSHIKI Masashi The University of Tokyo, Faculty of Medicine, Research Associate, 医学部附属病院, 助手 (70302734)
ANDO Katsuyuki The University of Tokyo, Health Care Centre, Lecturer, 保健センター, 講師 (60184313)
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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 |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2005: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2004: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Oxidative stress / adrenomedullin / Metabolic syndrome / glucose / aldosterone / platinum / 交感神経 / 肥満 / 加齢 |
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| Research Abstract |
In the present study, we used adrenomedullin deficient mice to study the role of oxidative stress in metabolic syndrome and possible therapeutic effect of antioxidants. We tested, the effect of dominant negative IkB (DNIkB), adrenomedullin and platinum nano-colloid particle as antioxidants in liver injury and vascular injury. We formerly reported that adrenomedullin deficient mice has higher oxidative stress and shows insulin resistance and vascular damages. In the present study, we firstly investigated the mechanism of adrenomedullin to inhibit oxidative stress. Adrenomedullin inhibited Src phosphorylation and thus inhibited angiotensin II-induced NADPH oxidase activation. Also adrenomedullin can inhibit oxidative stress induced by high glucose or aldosterone. Then we studied the possible antioxidant therapy in vivo. Liver injury was induced by lipopolysaccharide administration in adrenomedullin deficient mice and DNIkB successfully inhibited oxidative stress-induced NFkB activation and thus protected liver from damages. Platinum nano-colloid was administered to dB/dB mice with angiotensin II loading which is a model of metabolic syndrome and shows coronary damages. Treatment with platinum reduced in situ oxidative stress for long term and reduced vascular damages. There still remains the issues to be solved in safety of platinum or DNIkB for long-term usage and so on, however, so far our study showed that targeting oxidative stress may be effective in protecting organs in metabolic syndrome.
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Report
(3 results)
Research Products
(36 results)
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[Journal Article] Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice.2006
Author(s)
Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, Fukuda T, Sato T, Sekine K, Kato S, Isshiki M, Fujita T, Kobayashi M, Kawamura K, Masuda H, Kamiya A, Ando J
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Journal Title
Nature Med 12
Pages: 133-137
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Impaired flow-dependent control of vascular tone and remodeling in P2X4-deficient mice.2006
Author(s)
Yamamoto K, Sokabe T, Matsumoto T, Yoshimura K, Shibata M, Ohura N, Fukuda T, Sato T, Sekine K, Kato S, Isshiki M, Fujita T, Kobayashi M, Kawamura K, Masuda H, Kamiya A, Ando J.
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Journal Title
Nature Med 12
Pages: 133-137
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet.2005
Author(s)
Kushiyama A, Shojima N, Ogihara T, Inukai K, Sakoda H, Fujishiro M, Fukushima Y, Anai M, Ono H, Horike N, Viana AY, Uchijima Y, Nishiyama K, Shimosawa T, Fujita T, Katagiri H, Oka Y, Kurihara H, Asano T
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Journal Title
J Biol Chem 280
Pages: 42016-25
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] A free-ranging roundtable discussion on hypertension.2005
Author(s)
Standridge JB, Sealey JE, Laragh JH, Houston MC, Gavras H, Johnson RJ, Blumenfeld JD, Brown M, Egan BM, Meltzer JI, Shimosawa T, Fujita T
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Journal Title
J Hum Hypertens. 17
Pages: 259-66
Description
「研究成果報告書概要(和文)」より
Related Report
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[Journal Article] Resistin like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes and induces diabetes, hyperlipidemia and fatty liver in transgenic mice on a high-fat diet.2005
Author(s)
Kushiyama A, Shojima N, Ogihara T, Inukai K, Sakoda H, Fujishiro M, Fukushima Y, Anai M, Ono H, Horike N, Viana AY, Uchijima Y, Nishiyama K, Shimosawa T, Fujita T, Katagiri H, Oka Y, Kurihara H, Asano T.
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Journal Title
J Biol Chem. 280
Pages: 42016-42025
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] A free-ranging roundtable discussion on hypertension.2005
Author(s)
Standridge JB, Sealey JE, Laragh JH, Houston MC, Gavras H, Johnson RJ, Blumenfeld JD, Brown M, Egan BM, Meltzer JI, Shimosawa T, Fujita T.
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Journal Title
J Hum Hypertens. 17
Pages: 259-266
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Resistin-like molecule beta activates MAPKs, suppresses insulin signaling in hepatocytes, and induces diabetes, hyperlipidemia, and fatty liver in transgenic mice on a high fat diet.2005
Author(s)
Kushiyama A, Shojima N, Ogihara T, Inukai K, Sakoda H, Fujishiro M, Fukushima Y, Anai M, Ono H, Horike N, Viana AY, Uchijima Y, Nishiyama K, Shimosawa T, Fujita T, Katagiri H, Oka Y, Kurihara H, Asano T.
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Journal Title
J Biol Chem 280
Pages: 42016-42025
Related Report
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