Department of Pediatrics, University of California-San Diego, La Jolla, California, USA.
Antioxid Redox Signal. 2012 May 15;16(10):1071-6. doi: 10.1089/ars.2011.4504. Epub 2012 Feb 23.
Prolonged hyperoxia exposure generates excessive reactive oxygen species (ROS) and potentially leads to oxidative injury in every organ. We have previously generated Drosophila melanogaster flies that tolerate extreme oxidative stress (90%-95% O₂), a lethal condition to naive flies, through a long-term laboratory selection. We found that hyperoxia-selected (S(O2)A) flies had a significantly longer lifespan in hyperoxia and paraquat-induced oxidative stress. Prolonged hyperoxia exposure induced a significant ROS accumulation and an increased expression of oxidative stress markers, including lipid peroxidation and protein carbonyl contents in control flies, but not in S(O2)A flies. Enzymatic assays revealed that antioxidant enzyme activity in S(O2)A flies was similar to that in control flies. However, in isolated mitochondria and using electron paramagnetic resonance, we observed that S(O2)A flies displayed a decreased superoxide yield during state 3 respiration as compared to control flies and that the activity of electron transport chain complex I and III was also inhibited in S(O2)A flies. Our observations lead to the hypothesis that decreased complex activity results in a decreased ROS production, which might be a major potential adaptive mechanism of hyperoxia tolerance.
长时间的高氧暴露会产生过多的活性氧（ROS），并可能导致每个器官的氧化损伤。我们之前通过长期的实验室选择，产生了能够耐受极端氧化应激（90%-95% O₂）的黑腹果蝇，这对原始果蝇来说是致命的条件。我们发现，经过高氧选择（S(O2)A）的果蝇在高氧和百草枯诱导的氧化应激中具有显著延长的寿命。长时间的高氧暴露会导致对照果蝇中 ROS 大量积累，并增加氧化应激标志物的表达，包括脂质过氧化和蛋白质羰基含量，但 S(O2)A 果蝇中则没有。酶活性测定显示，S(O2)A 果蝇中的抗氧化酶活性与对照果蝇相似。然而，在分离的线粒体中，使用电子顺磁共振，我们观察到 S(O2)A 果蝇在状态 3 呼吸期间的超氧化物产量比对照果蝇低，并且 S(O2)A 果蝇中的电子传递链复合物 I 和 III 的活性也受到抑制。我们的观察结果导致了一个假设，即复合物活性的降低导致 ROS 产生的减少，这可能是高氧耐受的一个主要潜在适应机制。
