Antioxidant function of a novel selenoprotein in Drosophila melanogaster
Antioxidant function of a novel selenoprotein in Drosophila melanogaster
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DOI：
10.1046/j.1365-2443.2003.00687.x
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发表时间：
2003-12-01
期刊：
影响因子：
2.1
通讯作者：
Berry, MJ
中科院分区：
文献类型：
--
作者：
Morozova, N;Forry, EP;Berry, MJ
背景：昆虫在抗氧化损伤的防御机制上似乎与高等生物和低等生物都有所不同。它们不编码谷胱甘肽过氧化物酶或谷胱甘肽还原酶，它们的硫氧还蛋白还原酶表现出与高等和低等物种不同的特性。然而，抗氧化剂和促氧化剂的适当平衡，以及对有害活性氧的保护，显然对昆虫的生存能力、信号通路的正常功能和形态发生至关重要，并且在果蝇和其他生物的寿命研究中也有涉及。结果：在黑胃果蝇中发现了两个新的硒蛋白dselH和dselK。我们使用RNAi在D. melanogaster胚胎和Schneider S2细胞中抑制这些蛋白的表达。我们报告抑制dselH或dselK的表达显著降低胚胎的生存能力。我们进一步表明，dselH沉默降低了胚胎和Schneider细胞的总抗氧化能力，并增加了细胞中的脂质过氧化。相反，dselH在细胞系中的瞬时表达可减少脂质过氧化，并逆转谷胱甘肽消耗药物的毒性作用。后者与节约谷胱甘肽水平有关。结论：这些研究表明硒蛋白在脊椎动物抗氧化防御中的众所周知的作用也延伸到包括无脊椎动物。
Background: Insects appear to have diverged from both higher and lower organisms in their defense mechanisms against oxidative damage. They do not encode glutathione peroxidases or glutathione reductases, and their thioredoxin reductases exhibit distinct properties from those of higher and lower species. Nonetheless, appropriate balance of anti-oxidants and pro-oxidants, and protection from damaging reactive oxygen species are clearly crucial in insects for viability, normal functioning of signalling pathways and morphogenesis, and have been implicated in studies on longevity in flies and other organisms.Results: Two novel selenoproteins, dselH and dselK, were recently identified in Drosophila melanogaster. We have used RNAi in D. melanogaster embryos and in Schneider S2 cells to inhibit expression of these proteins. We report that inhibition of either dselH or dselK expression significantly reduces viability in embryos. We further show that dselH silencing decreases total anti-oxidant capacity in embryos and Schneider cells, and increases lipid peroxidation in cells. Conversely, transient expression of dselH in the cell line decreases lipid peroxidation, and reverses the toxic effects of a glutathione-depleting drug. The latter correlates with sparing of glutathione levels.Conclusions: These studies suggest that the well-known role of selenoproteins in vertebrate anti-oxidant defenses also extends to include invertebrates.