MnSOD deficiency results in elevated oxidative stress and decreased mitochondrial function but does not lead to muscle atrophy during aging.
MnSOD deficiency results in elevated oxidative stress and decreased mitochondrial function but does not lead to muscle atrophy during aging.
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DOI：
10.1111/j.1474-9726.2011.00695.x
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发表时间：
2011-06
期刊：
影响因子：
7.8
通讯作者：
Van Remmen H
中科院分区：
文献类型：
--
作者：
Lustgarten MS;Jang YC;Liu Y;Qi W;Qin Y;Dahia PL;Shi Y;Bhattacharya A;Muller FL;Shimizu T;Shirasawa T;Richardson A;Van Remmen H
在以前的研究中，我们报告说，缺乏MnSOD活性（约80%的减少）针对IIB型骨骼肌纤维足以提高氧化应激和减少肌肉功能的年轻成年小鼠（TnIFastCreSod 2fl/fl小鼠）。在本研究中，我们使用TnIFastCreSod 2fl/fl小鼠来检查氧化应激升高对线粒体功能的影响，并测试TnIFastCreSod 2fl/fl小鼠寿命期间氧化应激升高和线粒体功能降低足以加速与衰老相关的肌肉萎缩的假设。我们发现，与对照小鼠相比，年轻和年老的TnIFastCreSod 2fl/fl小鼠的线粒体功能都降低了。复合物II活性在年轻的TnIFastCreSod 2fl/fl小鼠中降低了47%，在年老的TnIFastCreSod 2fl/fl小鼠中降低了约90%，这与复合物II、SDHA和SDHB的催化亚基水平降低有关。在年轻的TnIFastCreSod 2fl/fl小鼠中，复合物II相关的线粒体呼吸减少约70%。复合物II连接的线粒体ATP产生在年轻小鼠中减少了39%，并且发现在老年TnIFastCreSod 2fl/fl小鼠中几乎完全不存在。此外，在年老的TnIFastCreSod 2fl/fl小鼠中，乌头酸酶活性几乎完全消除;线粒体超氧化物释放保持高于2倍的升高;并且氧化损伤（测量为F2异前列烷）相对于年龄匹配的对照增加30%。这些数据表明，尽管骨骼肌特异性线粒体氧化应激、氧化损伤和复合物II相关的线粒体功能障碍升高，但老年TnIFastCreSod 2fl/fl小鼠中年龄相关的肌肉萎缩并未加速，表明线粒体氧化应激可能不是年龄相关的肌肉萎缩的原因。
In a previous study, we reported that a deficiency in MnSOD activity (approximately 80% reduction) targeted to type IIB skeletal muscle fibers was sufficient to elevate oxidative stress and to reduce muscle function in young adult mice (TnIFastCreSod2fl/fl mice). In the present study, we used TnIFastCreSod2fl/fl mice to examine the effect of elevated oxidative stress on mitochondrial function and to test the hypothesis that elevated oxidative stress and decreased mitochondrial function over the lifespan of the TnIFastCreSod2fl/fl mice would be sufficient to accelerate muscle atrophy associated with aging. We found that mitochondrial function is reduced in both young and old TnIFastCreSod2fl/fl mice, when compared with control mice. Complex II activity is reduced by 47% in young and by ~90% in old TnIFastCreSod2fl/fl mice, associated with reduced levels of the catalytic subunits for complex II, SDHA and SDHB. Complex II-linked mitochondrial respiration is reduced by approximately 70% in young TnIFastCreSod2fl/fl mice. Complex II-linked mitochondrial ATP production is reduced by 39% in young and was found to be almost completely absent in old TnIFastCreSod2fl/fl mice. Furthermore, in old TnIFastCreSod2fl/fl mice, aconitase activity is almost completely abolished; mitochondrial superoxide release remains greater than 2-fold elevated; and oxidative damage (measured as F2 isoprostanes) is increased by 30% relative to age-matched controls. These data show that despite elevated skeletal muscle-specific mitochondrial oxidative stress, oxidative damage and complex II-linked mitochondrial dysfunction, age-related muscle atrophy was not accelerated in old TnIFastCreSod2fl/fl mice, suggesting mitochondrial oxidative stress may not be causal for age-related muscle atrophy.
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DOI：
10.1093/gerona/63.12.1277
发表时间：
2008-12
期刊：
The journals of gerontology. Series A, Biological sciences and medical sciences
影响因子：
--
作者：
Feng J;Navratil M;Thompson LV;Arriaga EA
通讯作者：
Arriaga EA
影响因子：
2.9
作者：
Bulteau, AL;Ikeda-Saito, M;Szweda, LI
通讯作者：
Szweda, LI
影响因子：
1.5
作者：
BURKHOLDER, TJ;FINGADO, B;LIEBER, RL
通讯作者：
LIEBER, RL
HIF1Alpha调节环将缺氧和线粒体信号联系起来。
影响因子：
4.5
作者：
Dahia, PLM;Ross, KN;Wright, ME;Hayashida, CY;Santagata, S;Barontini, M;Kung, AL;Sanso, G;Powers, JF;Tischler, AS;Hodin, R;Heitritter, S;Moore, F;Dluhy, R;Sosa, JA;Ocal, IT;Benn, DE;Marsh, DJ;Robinson, BG;Schneider, K;Garber, J;Arum, SM;Korbonits, M;Grossman, A;Pigny, P;Toledo, SPA;Nosé, V;Li, C;Stiles, CD
通讯作者：
Stiles, CD
DOI：
10.1073/pnas.91.25.12248
发表时间：
1994-12-06
影响因子：
11.1
作者：
GARDNER, PR;NGUYEN, DDH;WHITE, CW
通讯作者：
WHITE, CW