A Putative Glutathione Peroxidase of Drosophila Encodes a Thioredoxin Peroxidase That Provides Resistance Against Oxidative Stress but Fails to Complement a Lack of Catalase Activity

Biol Chem. 2003 Mar;384(3):463-72. doi: 10.1515/BC.2003.052.

Abstract

Cellular defense systems against reactive oxygen species (ROS) include thioredoxin reductase (TrxR) and glutathione reductase (GR). They generate sulfhydryl-reducing systems which are coupled to antioxidant enzymes, the thioredoxin and glutathione peroxidases (TPx and GPx). The fruit fly Drosophila lacks a functional GR, suggesting that the thioredoxin system is the major source for recycling glutathione. Whole genome in silico analysis identified two non-selenium containing putative GPx genes. We examined the biochemical characteristics of one of these gene products and found that it lacks GPx activity and functions as a TPx. Transgene-dependent overexpression of the newly identified Glutathione peroxidase homolog with thioredoxin peroxidase activity (Gtpx-1) gene increases resistance to experimentally induced oxidative stress, but does not compensate for the loss of catalase, an enzyme which, like GTPx-1, functions to eliminate hydrogen peroxide. The results suggest that GTPx-1 is part of the Drosophila Trx antioxidant defense system but acts in a genetically distinct pathway or in a different cellular compartment than catalase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Base Sequence
  • Catalase / genetics
  • Catalase / metabolism*
  • Drosophila melanogaster / enzymology*
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • Genes, Insect / genetics
  • Glutathione Peroxidase / genetics*
  • Hyperoxia / physiopathology
  • In Situ Hybridization
  • Longevity / genetics
  • Molecular Sequence Data
  • Neoplasm Proteins*
  • Oxidative Stress* / drug effects
  • Oxidative Stress* / physiology
  • Paraquat / toxicity
  • Peroxidases / genetics*
  • Peroxiredoxins
  • Reactive Oxygen Species / metabolism
  • Sequence Alignment
  • Transgenes / genetics

Substances

  • Neoplasm Proteins
  • Reactive Oxygen Species
  • Peroxidases
  • Peroxiredoxins
  • Catalase
  • Glutathione Peroxidase
  • Paraquat