title: 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.
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.
authors.affiliation: Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg, D-37077 Göttingen, Germany.
authors.forename: Fanis
authors.initials: F
authors.lastname: Missirlis
authors.forename: Stefan
authors.initials: S
authors.lastname: Rahlfs
authors.forename: Nikolaos
authors.initials: N
authors.lastname: Dimopoulos
authors.forename: Holger
authors.initials: H
authors.lastname: Bauer
authors.forename: Katja
authors.initials: K
authors.lastname: Becker
authors.forename: Arthur
authors.initials: A
authors.lastname: Hilliker
authors.forename: John P
authors.initials: JP
authors.lastname: Phillips
authors.forename: Herbert
authors.initials: H
authors.lastname: Jäckle
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001483:Base Sequence; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000201:enzymology* / Q000235:genetics / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D017344:Genes, Insect / Q000235:genetics; D005979:Glutathione Peroxidase / Q000235:genetics*; D018496:Hyperoxia / Q000503:physiopathology; D017403:In Situ Hybridization; D008136:Longevity / Q000235:genetics; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D010269:Paraquat / Q000633:toxicity; D010544:Peroxidases / Q000235:genetics*; D054464:Peroxiredoxins; D017382:Reactive Oxygen Species / Q000378:metabolism; D016415:Sequence Alignment; D019076:Transgenes / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D017382:Reactive Oxygen Species; D010544:Peroxidases; D054464:Peroxiredoxins; D002374:Catalase; D005979:Glutathione Peroxidase; D010269:Paraquat