Oxidative stress and aging reduce COX I RNA and cytochrome oxidase activity in Drosophila.
Oxidative stress and aging reduce COX I RNA and cytochrome oxidase activity in Drosophila.
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DOI：
10.1016/s0891-5849(98)00153-1
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发表时间：
1998-10
影响因子：
7.4
通讯作者：
Steven R. Schwarze;R. Weindruch;J. Aiken
中科院分区：
文献类型：
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作者：
Steven R. Schwarze;R. Weindruch;J. Aiken
黑腹果蝇显示出与年龄相关的氧化损伤增加和线粒体转录物减少。为了确定这些变化是否会导致能量产生不足，我们测量了电子传递系统（ETS）酶活性和ATP水平随年龄的变化。年龄对复合物I和II或柠檬酸合酶的活性无统计学意义的影响。相比之下，羽化后2 ~ 45 d，复合体IV细胞色素c氧化酶活性（COX，下降40%）和ATP丰度（15%）下降，而脂质过氧化增加71%。接下来，我们研究了基因或化学氧化应激的果蝇，以确定对线粒体编码的细胞色素氧化酶I RNA （coxI）水平和COX活性的影响。与野生型相比，过氧化氢酶零突变系的coxI RNA含量为48%。铜锌超氧化物歧化酶（Cu/Zn superoxide dismutase, cSOD）阴性蝇coxI RNA下降速率大于对照组。CoxI RNA也随过氧化氢（H2O2）处理的增加而降低，表现为细胞色素c氧化酶（COX）活性的降低。这些结果表明，氧化应激与线粒体转录物水平的降低密切相关，并支持氧化应激可能导致黑腹龙线粒体功能障碍和衰老的假设。
Drosophila melanogaster displays an age-associated increase in oxidative damage and a decrease in mitochondrial transcripts. To determine if these changes result in energy production deficiencies, we measured the electron transport system (ETS) enzyme activity, and ATP levels with age. No statistically significant influences of age on activities of complexes I and II or citrate synthase were observed. In contrast, from 2 to 45 days post-eclosion, declines were found in complex IV cytochrome c oxidase activity (COX, 40% decline) and ATP abundance (15%), while lipid peroxidation increased 71%. We next examined flies that were either genetically or chemically oxidatively stressed to determine the effect on levels of mitochondrial-encoded cytochrome oxidase I RNA (coxI) and COX activity. A catalase null mutant line had 48% of coxI RNA compared to the wild type. In Cu/Zn superoxide dismutase (cSOD) null flies, the rate of coxI RNA decline was greater than in controls. CoxI RNA also declined with increasing hydrogen peroxide (H2O2) treatment, which was reflected in reduced cytochrome c oxidase (COX) activity. These results show that oxidative stress is closely associated with reductions in mitochondrial transcript levels and support the hypothesis that oxidative stress may contribute to mitochondrial dysfunction and aging in D. melanogaster.