2004 Fiscal Year Final Research Report Summary
Non-invasive analysis of dynamic state of reactive oxygen species in tissue and blood vessel of circulatory diseases
| Project/Area Number |
14207105
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
応用薬理学・医療系薬学
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| Research Institution | Kyushu University |
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Principal Investigator |
UTSUMI Hideo KYUSHU UNIVERSITY, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (20101694)
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| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Akira KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Emeritus Professor, 大学院・医学研究院, 名誉教授 (30038814)
YASUI Hisataka KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Emeritus Professor, 大学院・医学研究院, 名誉教授 (20089923)
KOGA Noboru KYUSHU UNIVERSITY, Graduate School of Pharmaceutical Sciences, Professor, 大学院・薬学研究院, 教授 (60161890)
HIRATA Hiroshi Yamagata University, Department of Engineering, Associate Professor, 工学部, 助教授 (60250958)
INOGUCHI Toyoshi KYUSHU UNIVERSITY, Graduate School of Medical Sciences, Assistant Professor, 大学院・医学研究院, 講師 (00294926)
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| Project Period (FY) |
2002 – 2004
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| Keywords | reactive oxygen species / free radical / electron spin resonance / diabetes / obese / nitroxyl radical |
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| Research Abstract |
It is reported that reactive oxygen species (ROS) are involved in the initiation and/or progression of circulatory diseases. In order to analyze is vivo ROS generation non-invasively, we developed the In vivo spin electron resonance (ESP)/spin probe technique using a signal decay rate of a nitroxyl radical as an index of ROS generation and clarified the association of ROS generation with several diseases in experimental animals.
In this study, we performed non-invasive measurement of ROS generation in the models of diabetes and obese as representative circulatory diseases. When carbamoyl-PROXYL solution, which is one of nitroxyl radicals, was administered intravenously to the disease group, the signal decay rate of carbamoyl-PROXYL was enhanced compared with the control group. The enhancement was suppressed by SOD and α-tocopherol, suggesting that the enhancement of signal decay in the disease group is due to ROS generation in blood vessels. Furthermore, the enhancement was suppressed b
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y protein kinase C inhibitor, CGP41251 and NADPH oxidase inhibitor, apocinin, suggesting that ROS generation is derived from NADPH oxidase in the blood vessels.
It is essential to investigate ROS generates in what organ or tissue of experimental animals, we built the ESRI/MRI fusion system. Nitroxyl radicals with different membrane permeability were intravenously administered to mice, and then the ESRI/MRI measurement was performed. The difference of the spin dynamic state between nitroxyl radicals distributing in blood vessels and those in not only blood vessels but also tissues were clarified using this imaging system.
We newly synthesized several kinds of 15N-labeled nitroxyl radicals and ^<15>N, D-labeled nitroxyl radicals in order to improve ESR sensitivity. Furthermore, we developed the automatic tuning control(ATC) and the automatic matching control(AMC) for the purpose of the suppression of respiratory or beating noise and evaluated the control characteristics in in vivo ESR measurement.
We clarified the ROS generation in blood vessels of animal models of diabetes or obese. In the near future, the image analysis of ROS dynamic state with high sensitivities by the application of the ESRI/MRI fusion system and the newly synthesized probes would be clarified the ROS generation in the initiation and/or progression of circulatory diseases. Less
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[Journal Article] Overexpression of glutathione peroxidase prevents left ventricular remodeling and failure after myocardial infarction in mice.2004
Author(s)
Shiomi, T., Tsutsui, H., Matsusaka, H., Murakami, K., Hayashidani, S., Ikeuchi, M., Wen, J., Kubota, T., Utsumi, H., Takeshita, A.
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Journal Title
Circulation 109
Pages: 544-549
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Nox4 as the major catalytic component of an endothelial NAD(P)H oxidase.2004
Author(s)
Ago, T., Kitazono, T., Ooboshi, H., Iyama, T., Han, Y.H., Takada, J., Wakisaka, M., Ibayashi, S., Utsumi, H., Iida, M.
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Journal Title
Circulation 109
Pages: 227-233
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Evidence for contribution of vascular NAD(P)H oxidase to increased oxidative stress in animal models of diabetes and obesity2004
Author(s)
Sonta, T, Inoguchi, T, Tsubouchi, H, Sekiguchi, N, Kobayashi, K, Matsumoto, S, Utsumi, H, Nawata, H
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Journal Title
FREE RADICAL BIOLOGY AND MEDICINE 37(1)
Pages: 115-123
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Evidence for contribution of vascular NAD(P)H oxidase to increased oxidative stress in animal models of diabetes and obesitv2004
Author(s)
Sonta, T, Inoguchi, T, Tsubouchi, H, Sekiguchi, N, Kobayashi, K, Matsumoto, S, Utsumi, H, Nawata, H
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Journal Title
Free Radic Biol Med 37
Pages: 115-123
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Association between the expression of inducible nitric oxide synthase by chondrocytes and its nitric oxide-generating activity in adjuvant arthritis in rats.2003
Author(s)
Yonekura, Y., Koshiishi, I., Yamada, K., Mori, A., Uchida, S., Nakamura, T., Utsumi, H.
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Journal Title
Nitric Oxide 8
Pages: 164-169
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Overexpression of tumor necrosis factor-alpha increases production of hydroxyl radical in murine myocardium.2003
Author(s)
Machida, Y., Kubota, T., Kawamura, N., Funakoshi, H., Ide, T., Utsumi, H., Li, Y.Y., Feldman, A.M., Tsutsui, H., Shimokawa, H., Takeshita, A
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Journal Title
Am J Physiol Heart Circ Physiol 284
Pages: H449-H455
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Protein kinase C-dependent increase in reactive oxygen species (ROS) production in vascular tissues of diabetes : role of vascular NAD(P)H oxidase.2003
Author(s)
Inoguchi, T., Sonta, T., Tsubouchi, H., Etoh, T., Kakimoto, M., Sonoda, N., Sato, N., Sekiguchi, N., Kobayashi, K., Sumimoto, H., Utsumi, H., Nawata, H.
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Journal Title
J Am Soc Nephrol 14
Pages: S227-S232
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Probucol attenuates left ventricular dysfunction and remodeling in tachycardia-induced heart failure : roles of oxidative stress and inflammation.2002
Author(s)
Nakamura, R., Egasira, K., Machida, Y., Hayashidani, S., Takeya, M., Utsumi, H., Tsutsui, H., Takeshita, A.
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Journal Title
Circulation 106
Pages: 362-367
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Amyloid-beta-protein (A beta)(25-35)-associated free radical generation is strongly influenced by the aggregational state of the peptides2002
Author(s)
Monji, A., Utsumi, H., Ueda, T., Imoto, T., Yoshida, I., Hashioka, S., Tashiro, K., Tashiro, N
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Journal Title
Life Science 70
Pages: 833-841
Description
「研究成果報告書概要(和文)」より
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[Journal Article] Probucol attenuates left ventricular dysfunction and remodeling in tachycardia-induced heart failure : roles of oxidative stress and inflammation.2002
Author(s)
Nakamura, R., Egashira, K., Machida, Y., Hayashidani, S., Takeya, M., Utsumi, H., Tsutsui, H., Takeshita, A.
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Journal Title
Circulation 106
Pages: 362-367
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Amyloid-beta-protein (A beta) (25-35)-associated free radical generation is strongly influenced by the aggregational state of the peptides2002
Author(s)
Monji, A., Utsumi, H., Ueda, T., Imoto, T., Yoshida, I., Hashioka, S., Tashiro, K., Tashiro, N
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Journal Title
Life Science 70
Pages: 833-841
Description
「研究成果報告書概要(欧文)」より
