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Antioxidants Improve the Phenotypes of Dilated Cardiomyopathy and Muscle Fatigue in Mitochondrial Superoxide Dismutase-Deficient Mice
Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan
Department of Orthopaedics, Juntendo University School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan
Molecular Gerontology, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo 173-0015, Japan
Research Laboratories for Applied Technology of Food, Asahi Group Holdings, Ltd., Ibaraki 302-0106, Japan
Department of Ageing Control Medicine, Juntendo University Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan
* Author to whom correspondence should be addressed.
Received: 10 December 2012; in revised form: 14 January 2013 / Accepted: 16 January 2013 / Published: 24 January 2013
Abstract: Redox imbalance elevates the reactive oxygen species (ROS) level in cells and promotes age-related diseases. Superoxide dismutases (SODs) are antioxidative enzymes that catalyze the degradation of ROS. There are three SOD isoforms: SOD1/CuZn-SOD, SOD2/Mn-SOD, and SOD3/EC-SOD. SOD2, which is localized in the mitochondria, is an essential enzyme required for mouse survival, and systemic knockout causes neonatal lethality in mice. To investigate the physiological function of SOD2 in adult mice, we generated a conditional Sod2 knockout mouse using a Cre-loxP system. When Sod2 was specifically deleted in the heart and muscle, all mice exhibited dilated cardiomyopathy (DCM) and died by six months of age. On the other hand, when Sod2 was specifically deleted in the skeletal muscle, mice showed severe exercise disturbance without morphological abnormalities. These provide useful model of DCM and muscle fatigue. In this review, we summarize the impact of antioxidants, which were able to regulate mitochondrial superoxide generation and improve the phenotypes of the DCM and the muscle fatigue in mice.
Keywords: manganese superoxide dismutase (Mn-SOD); mitochondria; dilated cardiomyopathy (DCM); EUK-8; procyanidins
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Koyama, H.; Nojiri, H.; Kawakami, S.; Sunagawa, T.; Shirasawa, T.; Shimizu, T. Antioxidants Improve the Phenotypes of Dilated Cardiomyopathy and Muscle Fatigue in Mitochondrial Superoxide Dismutase-Deficient Mice. Molecules 2013, 18, 1383-1393.
Koyama H, Nojiri H, Kawakami S, Sunagawa T, Shirasawa T, Shimizu T. Antioxidants Improve the Phenotypes of Dilated Cardiomyopathy and Muscle Fatigue in Mitochondrial Superoxide Dismutase-Deficient Mice. Molecules. 2013; 18(2):1383-1393.
Koyama, Hirofumi; Nojiri, Hidetoshi; Kawakami, Satoru; Sunagawa, Tadahiro; Shirasawa, Takuji; Shimizu, Takahiko. 2013. "Antioxidants Improve the Phenotypes of Dilated Cardiomyopathy and Muscle Fatigue in Mitochondrial Superoxide Dismutase-Deficient Mice." Molecules 18, no. 2: 1383-1393.