2010 Fiscal Year Final Research Report
Oxidative stress in skeletal muscle causes severe disturbance of exercise activity
| Project/Area Number |
20500641
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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 |
Applied health science
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| Research Institution | Tokyo Metropolitan Institute of Gerontology |
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Principal Investigator |
SHIMIZU Takahiko Tokyo Metropolitan Institute of Gerontology, 東京都健康長寿医療センター研究所, 研究員 (40301791)
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| Project Period (FY) |
2008 – 2010
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| Keywords | 骨格筋 / 酸化ストレス / 運動器老化 / ミトコンドリア / モデルマウス |
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| Research Abstract |
The increase in reactive oxygen species (ROS) levels that occurs during intense exercise has been proposed to be one of the major causes of muscle fatigue. To investigate the pathological significance of oxidative stress in skeletal muscle, we generated skeletal muscle-specific manganese superoxide dismutase (Mn-SOD)-deficient (muscle-Sod2^<-/->) mice. The mutant mice showed severe disturbances in exercise activity, but no atrophic changes in their skeletal muscles. In histological and histochemical analyses, the mutant mice showed centralized nuclei in their muscle fibers and selective loss of enzymatic activity in mitochondrial respiratory chain complexes. In addition, the mutant mice displayed increased oxidative damage and reduced ATP content in their muscle tissue. Furthermore, a single administration of the antioxidant EUK-8 significantly improved exercise activity and increased the cellular ATP level in skeletal muscle. These results imply that the superoxide anions generated in mitochondria play a pivotal role in the progression of exercise intolerance.
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[Journal Article] Antioxidant therapy attenuates myocardial telomerase activity reduction in superoxide dismutase-deficient mice.2011
Author(s)
Makino, N., Maeda, T., Oyama, J.I., Sasaki, M., Higuchi, Y., Mimori, K. Shimizu, T.
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Journal Title
J Mol Cell Cardiol 50
Pages: 670-677
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[Journal Article] MnSOD deficiency results in elevated oxidative stress and decreased mitochondrial function but does not lead to muscle atrophy during aging.2011
Author(s)
Lustgarten, M.S., Jang, Y.C., Liu, Y., Qi, W., Qin, Y., Dahia, P.L., Shi, Y., Bhattacharya, A., Muller, F.L., Shimizu, T., Shirasawa, T., Richardson, A. Van Remmen, H.
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Journal Title
Aging Cell 10
Pages: 493-505
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[Journal Article] Superoxide dismutase deficiency enhances superoxide levels in brain tissues during oxygenation and hypoxia-reoxygenation.2011
Author(s)
Sasaki, T., Shimizu, T., Koyama, T., Sakai, M., Uchiyama, S., Kawakami, S., Noda, Y., Shirasawa, T., Kojima, S.
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Journal Title
J Neurosci Res 89
Pages: 601-610
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[Journal Article] Oxidative stress in skeletal muscle causes severe disturbance of exercise activity without muscle atrophy.2010
Author(s)
Kuwahara, H., Horie, T. Ishikawa, S. Tsuda, C., Kawakami, S., Noda, Y., Kaneko, T., Tahara, S., Tachibana, T., Okabe, M., Melki, J., Takano, R., Toda, T., Morikawa, D., Nojiri, H., Kurosawa, H., Shirasawa, T., Shimizu, T.
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Journal Title
Free Rad Biol Med 48
Pages: 1252-1262
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[Journal Article] Conditional knockout of MnSOD targeted to type IIB skeletal muscle fibers increases oxidative stress and is sufficient to alter aerobic exercise capacity.2009
Author(s)
Lustgarten, M., Jang, Y., Liu, Y., Muller, F., Qi, W., Steinhelper, M., Brooks, S., Larkin, L. M., Shimizu, T., Shirasawa, T., McManus, L., Bhattacharya, A., Richardson, A., Van Remmen, H.
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Journal Title
Am J Physiol 297
Pages: 1520-1532
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[Journal Article] Antioxidant, EUK-8, prevents murine dilated cardiomyopathy.2009
Author(s)
Kawakami, S., Matsuda, A., Sunagawa, T., Noda, Y., Kaneko, T., Tahara, S., Hiraumi, Y., Adachi, S., Matsui, H., Ando, K., Fujita, T., Maruyama, N., Shirasawa, T., Shimizu, T.
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Journal Title
Cir J 73
Pages: 2125-2134
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[Journal Article] Skin atrophy in cytoplasmic SOD-deficient mice and its complete recovery using a vitamin Cderivative.2009
Author(s)
Murakami, K., Inagaki, J., Saito, M., Ikeda, Y., Tsuda, C., Noda, Y., Kawakami, S., Shirasawa, T., Shimizu, T.
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Journal Title
Biochem Biophys Res Commun 382
Pages: 457-61
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[Journal Article] Retinal dysfunction and progressive retinal cell death in SOD1-deficient mice.2008
Author(s)
Hashizume, K., Hirasawa, M., Imamura, Y., Noda, S., Shimizu, T., Shinoda, K., Kurihara, T., Noda, K., Ozawa, Y., Ishida, S., Miyake, Y., Shirasawa, T., Tsubota, K.
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Journal Title
Am J Pathol 172
Pages: 1325-1331
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[Presentation] Intracellular superoxide dismutase deficiency decreased bone mass in vivo by impairment of cell viability and redox balance in osteoblasts.2010
Author(s)
Saita, Y.Nojiri, H.Tsuda, C.Miyazaki, T.Morikawa, D., Kaneko, K.Shimizu, T.
Organizer
The 32th Annual Meeting, The American Society for Bone and Mineral Research (ASBMR), Tronto
Place of Presentation
Canada
Year and Date
20101015-20101019
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[Remarks] ホームページ等
