Ataxia telangiectasia mutated influences cytochrome c oxidase activity
Ataxia telangiectasia mutated influences cytochrome c oxidase activity
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DOI：
10.1016/j.bbrc.2011.01.075
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发表时间：
2011-02-25
影响因子：
3.1
通讯作者：
Fisher, Jonathan S.
中科院分区：
文献类型：
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作者：
Patel, Akshar Y.;McDonald, Todd M.;Fisher, Jonathan S.
缺乏共济失调毛细血管扩张突变（ATM）的细胞线粒体功能受损。此外，缺乏ATM的哺乳动物细胞具有增加的活性氧（ROS）水平以及编码细胞色素c氧化酶（考克斯）的区域中的线粒体DNA（mtDNA）缺失。我们假设ATM特异性地影响骨骼肌中的考克斯活性。ATM缺陷小鼠胫骨前肌中的考克斯活性比野生型小鼠低40%（P < 0.01，n = 9/组）。然而，有没有ATM相关的差异，琥珀酸脱氢酶，异柠檬酸脱氢酶，α-酮戊二酸脱氢酶，线粒体甘油3-磷酸脱氢酶，或复合物III的活性。与仅用载体孵育的肌肉相比，用ATM抑制剂KU 55933孵育野生型趾长伸肌1小时导致考克斯活性降低50%（P < 0.05，n = 5/组）。在对照组和ATM抑制剂处理组中，考克斯酶活性与葡萄糖6-磷酸脱氢酶活性相关（r = 0.61，P < 0.05），葡萄糖6-磷酸脱氢酶是通过产生NADPH进行抗氧化防御的关键决定因素。总的来说，研究结果表明ATM对考克斯活性具有保护作用。(C)2011 Elsevier Inc. All rights reserved.
Cells lacking ataxia telangiectasia mutated (ATM) have impaired mitochondrial function. Furthermore, mammalian cells lacking ATM have increased levels of reactive oxygen species (ROS) as well as mitochondrial DNA (mtDNA) deletions in the region encoding for cytochrome c oxidase (COX). We hypothesized that ATM specifically influences COX activity in skeletal muscle. COX activity was similar to 40% lower in tibialis anterior from ATM-deficient mice than for wild-type mice (P < 0.01, n = 9/group). However, there were no ATM-related differences in activity of succinate dehydrogenase, isocitrate dehydrogenase, alpha-ketoglutarate dehydrogenase, mitochondrial glycerol 3-phosphate dehydrogenase, or complex III. Incubation of wild-type extensor digitorum longus muscles for 1 h with the ATM inhibitor KU55933 caused a similar to 50% reduction (P < 0.05, n = 5/group) in COX activity compared to muscles incubated with vehicle alone. Among the control muscles and muscles treated with the ATM inhibitor, COX activity was correlated (r = 0.61, P < 0.05) with activity of glucose 6-phosphate dehydrogenase, a key determinant of antioxidant defense through production of NADPH. Overall, the findings suggest that ATM has a protective role for COX activity. (C) 2011 Elsevier Inc. All rights reserved.