Department of Biology, Saint Louis University, St Louis, MO 63103, USA.
Biochem Biophys Res Commun. 2011 Feb 25;405(4):599-603. doi: 10.1016/j.bbrc.2011.01.075. Epub 2011 Jan 23.
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 ∼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 1h with the ATM inhibitor KU55933 caused a ∼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.
缺乏共济失调毛细血管扩张突变基因（ATM）的细胞线粒体功能受损。此外，缺乏 ATM 的哺乳动物细胞中活性氧（ROS）水平增加，以及编码细胞色素 c 氧化酶（COX）的线粒体 DNA（mtDNA）缺失。我们假设 ATM 特异性影响骨骼肌中的 COX 活性。与野生型小鼠相比，ATM 缺陷型小鼠的比目鱼肌中的 COX 活性降低了约 40%（P<0.01，n=9/组）。然而，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 ATM 无关。与单独用载体孵育相比，用 ATM 抑制剂 KU55933 孵育野生型伸趾长肌 1 小时会导致 COX 活性降低约 50%（P<0.05，n=5/组）。在对照肌肉和用 ATM 抑制剂处理的肌肉中，COX 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 来决定抗氧化防御的关键决定因素。总的来说，这些发现表明 ATM 对 COX 活性具有保护作用。
