Regulatory role of dADAR in ROS metabolism in Drosophila CNS

Brain Res Mol Brain Res. 2004 Nov 24;131(1-2):93-100. doi: 10.1016/j.molbrainres.2004.08.013.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenosine Deaminase / genetics*
  • Adenosine Deaminase / metabolism*
  • Animals
  • Cytochrome P-450 Enzyme System / genetics
  • Drosophila Proteins / genetics
  • Drosophila melanogaster / genetics*
  • Drosophila melanogaster / metabolism*
  • Free Radical Scavengers / metabolism
  • Ganglia, Invertebrate / metabolism
  • Gene Expression Regulation / physiology
  • Membrane Proteins / genetics
  • Mutation
  • Nervous System / metabolism
  • RNA Editing
  • RNA Precursors / metabolism
  • RNA-Binding Proteins
  • Reactive Oxygen Species / metabolism*
  • Thioredoxins / genetics

Substances

  • DHD protein, Drosophila
  • Drosophila Proteins
  • Free Radical Scavengers
  • Membrane Proteins
  • RNA Precursors
  • RNA-Binding Proteins
  • Reactive Oxygen Species
  • Thioredoxins
  • Cytochrome P-450 Enzyme System
  • ADARB1 protein, human
  • Adenosine Deaminase