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

Molecules

Hirofumi Koyama¹  Hidetoshi Nojiri¹  Satoru Kawakami¹  Tadahiro Sunagawa¹  Takuji Shirasawa¹ 

[1] ¹Department of Advanced Aging Medicine, Chiba University Graduate School of Medicine, Chiba 260-8670, Japan

关键词: manganese superoxide dismutase (Mn-SOD);    mitochondria;    dilated cardiomyopathy (DCM);    EUK-8;    procyanidins;   

DOI  :  10.3390/molecules18021383

来源: mdpi

【 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.

【 授权许可】

CC BY   
This is an open access article distributed under the Creative Commons Attribution License (CC BY) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.