Chen Li, Rio Donald C, Haddad Gabriel G, Ma Enbo
Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA.
Brain Res Mol Brain Res. 2004 Nov 24;131(1-2):93-100. doi: 10.1016/j.molbrainres.2004.08.013.
Pre-mRNA adenosine deaminase (ADAR) is involved in many physiological processes by either directly converting adenosine to inosine in certain pre-mRNAs or indirectly regulating expression of certain genes. Mutations of Drosophila ADAR (dADAR) results in neuronal dysfunction and hypersensitivity to oxygen deprivation. Recently, we found that the mutant flies were very resistant to paraquat, a compound that generates free radicals. In order to further characterize the neuronal role of dADAR and understand the basis for the resistance to the oxidative stress, we investigated the effect of dADAR on the expression of genes encoding scavengers of cellular reactive oxygen species (ROS) in both dADAR mutant and overexpression flies. Our data show that the expression of the genes encoding known ROS scavengers [superoxide dismutase (SOD) and catalase] is not regulated by dADAR. However, the transcripts of genes encoding two potential ROS scavengers (dhd and Cyp4g1) were robustly increased in dADAR mutant flies, and conversely both were significantly decreased in dADAR overexpressing flies. Using dhd [encoding a Drosophila homolog of the mammalian protein thioredoxin (Trx)] transgenic flies, we confirmed that the resistance of dADAR mutant flies to paraquat resulted, at least partially, from the up-regulation of dhd gene in dADAR mutant flies. Our data not only confirm the importance of ADAR in maintenance of neuronal function but also reveal its regulatory role in the expression of genes encoding ROS scavengers.
前体mRNA腺苷脱氨酶（ADAR）通过直接将某些前体mRNA中的腺苷转化为肌苷或间接调节某些基因的表达参与许多生理过程。果蝇ADAR（dADAR）的突变会导致神经元功能障碍和对缺氧的超敏反应。最近，我们发现突变果蝇对百草枯（一种产生自由基的化合物）具有很强的抗性。为了进一步表征dADAR在神经元中的作用并了解其对氧化应激抗性的基础，我们研究了dADAR对dADAR突变体和过表达果蝇中编码细胞活性氧（ROS）清除剂的基因表达的影响。我们的数据表明，编码已知ROS清除剂[超氧化物歧化酶（SOD）和过氧化氢酶]的基因表达不受dADAR调节。然而，编码两种潜在ROS清除剂（dhd和Cyp4g1）的基因转录本在dADAR突变果蝇中显著增加，相反，在dADAR过表达果蝇中两者均显著降低。使用dhd[编码哺乳动物蛋白硫氧还蛋白（Trx）的果蝇同源物]转基因果蝇，我们证实dADAR突变果蝇对百草枯的抗性至少部分源于dADAR突变果蝇中dhd基因的上调。我们的数据不仅证实了ADAR在维持神经元功能中的重要性，还揭示了其在编码ROS清除剂的基因表达中的调节作用。
