2006 Fiscal Year Final Research Report Summary
Analysis of heart/muscle-specific Mn-SOD-deficient mice.
| Project/Area Number |
17390085
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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 |
General medical chemistry
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| Research Institution | Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare |
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Principal Investigator |
SHIRASAWA Takuji Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Team Leader, 東京都老人総合研究所, 研究部長 (80226323)
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| Co-Investigator(Kenkyū-buntansha) |
SHIMIZU Yakahiko Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research Scientist, 東京都老人総合研究所, 研究員 (40301791)
TAKAHASHI Mayumi Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research Assistant, 東京都老人総合研究所, 助手 (50133632)
OGAWARA Midori Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research Assistant, 東京都老人総合研究所, 助手 (60100111)
MORIIZUMI Eiko Tokyo Metropolitan Foundation for Research on Aging and Promotion of Human Welfare, Research Assistant, 東京都老人総合研究所, 助手 (20322711)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Mn-SOD / Superoxide / Aging / Mitochondria / Cre-loxP / Respiratory complex / Apoptosis / ATP synthesis |
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| Research Abstract |
Elderly people insidiously manifest the symptoms of heart failure, such as dyspnea and/or physical disabilities in an age-dependent manner. Although previous studies suggested that oxidative stress plays a pathological role in the development of heart failure, no direct evidence has been documented so far. In order to investigate the pathological significance of oxidative stress in the heart, we generated heart/muscle-specific manganese superoxide dismutase (MnSOD)-deficient mice. The mutant mice developed progressive congestive heart failure with specific molecular defects in mitochondrial respiration. In this paper, we showed for the first time that the oxidative stress caused specific morphological changes of mitochondria, excess formation of superoxide (O2^<・->), reduction of ATP, and transcriptional alterations of genes associated with heart failure in respect to cardiac contractility. Accordingly, administration of an SOD mimetic significantly ameliorated the symptoms. These results implied that O2^<・-> generated in mitochondria played a pivotal role in the development and progression of heart failure. We here present a bona fide model for human cardiac failure with oxidative stress valuable for therapeutic interventic interventions.
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