Antioxidants Improve the Phenotypes of Dilated Cardiomyopathy and Muscle Fatigue in Mitochondrial Superoxide Dismutase-Deficient Mice

被引：39

作者：

Koyama, Hirofumi ^{[1
]}

Nojiri, Hidetoshi ^{[2
]}

Kawakami, Satoru ^{[3
]}

Sunagawa, Tadahiro ^{[4
]}

Shirasawa, Takuji ^{[5
]}

Shimizu, Takahiko ^{[1
,3
]}

机构：

[1] Chiba Univ, Dept Adv Aging Med, Grad Sch Med, Chiba 2608670, Japan

[2] Juntendo Univ, Dept Orthopaed, Sch Med, Bunkyo Ku, Tokyo 1138421, Japan

[3] Tokyo Metropolitan Inst Gerontol, Itabashi Ku, Tokyo 1730015, Japan

[4] Asahi Grp Holdings Ltd, Res Labs Appl Technol Food, Ibaraki 3020106, Japan

[5] Juntendo Univ, Dept Ageing Control Med, Grad Sch Med, Bunkyo Ku, Tokyo 1130033, Japan

来源：

MOLECULES | 2013年 / 18卷 / 02期

关键词：

manganese superoxide dismutase (Mn-SOD); mitochondria; dilated cardiomyopathy (DCM); EUK-8; procyanidins; LIFE-SPAN; CAENORHABDITIS-ELEGANS; OXIDATIVE STRESS; HEART-FAILURE; CATALASE MIMETICS; FREE-RADICALS; MUTANT MICE; RAT; CARVEDILOL; PORPHYRIN;

D O I：

10.3390/molecules18021383

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1383 / 1393

页数：11

共 34 条

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[34] Reduction of Mitochondrial ROS by Overexpression (OE) of Antioxidants Superoxide Dismutase 2 (SOD2) and Catalase Increases Muscle Glucose Uptake (MGU) during Exercise (EX) in Chow- and High Fat (HF)-Fed Mice In Vivo
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