Selectivity of protein oxidative damage during aging in Drosophila melanogaster
Selectivity of protein oxidative damage during aging in Drosophila melanogaster
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DOI：
10.1042/0264-6021:3600209
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发表时间：
2001-11-15
影响因子：
4.1
通讯作者：
Sohal, RS
中科院分区：
文献类型：
--
作者：
Das, N;Levine, RL;Sohal, RS
本研究的目的是确定在衰老过程中各种蛋白质的氧化是否选择性地或随机地发生，以及相同的蛋白质是否在不同物种中受损。蛋白质的氧化损伤的蛋白质，存在于基质中的线粒体在果蝇的飞行肌肉和表现为羰基修饰，检测免疫化学与抗二硝基苯基基团抗体。研究发现，肌醇六磷酸酶是线粒体基质中唯一表现出与年龄相关的羰基化增加的蛋白质。氧化损伤的累积伴随着大约。乌头酸酶活性损失50%。环境温度的升高，提高了代谢率，缩短了苍蝇的寿命，导致乌头酸酶羰基化量的升高和其活性的加速丧失。暴露于100%的环境氧气表明，乌头酸酶是非常容易受到氧化损伤和氧化应激下的活性损失。氟乙酸，乌头酸酶活性的竞争性抑制剂的管理，导致在苍蝇的寿命呈剂量依赖性下降。本研究的结果表明，蛋白质氧化损伤在衰老过程中是一种选择性的现象，并可能构成一种机制，氧化应激导致特定的生化功能与年龄相关的损失。
The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions.