title: The activity and hydrogen peroxide sensitivity of the peroxiredoxins from the parasitic nematode Haemonchus contortus.
abstract: The requirement of aerobic organisms to control damage caused by reactive oxygen species has led to the evolution of the antioxidant systems. Peroxiredoxins are a large family of peroxidases which detoxify hydrogen peroxide at the expense of thiols. The parasitic nematode Haemonchus contortus contains two peroxiredoxins, HcPrx1 a mitochondrial protein and HcPrx2 a cytoplasmic protein. Although both peroxiredoxins contain the conserved eukaryotic motifs 'GGLG' and 'YF', identified as critical for hydrogen peroxide instability, both were stable to high concentrations of hydrogen peroxide, demonstrating different functions to their mammalian counterparts. H. contortus also contains two thioredoxin reductases and five different thioredoxin-like proteins. The activity of both peroxiredoxins was specific for the thioredoxin system; however, both could also be regenerated by the glutathione system when coupled to the nematode specific thioredoxin HcTrx5. Analysis of homologous genes in Caenorhabditis elegans showed that only CePrx2, which is secreted, was sensitive to the external oxidant hydrogen peroxide. However, both peroxiredoxins KO C. elegans were sensitive to intracellular free radicals and both peroxiredoxins protected DNA from free radical attack. The results demonstrate that the hydrogen peroxide detoxification and the antioxidant activity of the peroxiredoxins are separate activities that are independent of the 'GGLG' and 'YF' motifs.
authors.affiliation: Institute for the Biotechnology of Infectious Diseases, University of Technology, Sydney, PO Box 123, Broadway NSW 2007, Australia.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Hudson
authors.forename: Irene M
authors.initials: IM
authors.lastname: Sotirchos
authors.forename: Mary W
authors.initials: MW
authors.lastname: Davey
mesh_terms: D020816:Amino Acid Motifs / Q000235:genetics; D000595:Amino Acid Sequence; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D006189:Haemonchus / Q000201:enzymology*; D006540:Herbicides / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000378:metabolism* / Q000494:pharmacology; D007700:Kinetics; D008969:Molecular Sequence Data; D016877:Oxidants / Q000494:pharmacology; D018384:Oxidative Stress; D010269:Paraquat / Q000494:pharmacology; D054464:Peroxiredoxins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D010802:Phylogeny; D016415:Sequence Alignment; D013879:Thioredoxins / Q000378:metabolism
chemical_list: D000975:Antioxidants; D006540:Herbicides; D016877:Oxidants; D013879:Thioredoxins; D006861:Hydrogen Peroxide; D054464:Peroxiredoxins; D010269:Paraquat