Source: http://cegg.unige.ch/insecta/immunodb/
PRDXs: Peroxidases
Summary

Carolina Barillas Mury 

Laboratory of Malaria and Vector Research, Twinbrook III Facility, NIAID, NIH, USA 

Local generation of high levels of reactive oxygen species (ROS) is an important effector mechanism during an immune response. For example, myeloperoxidase (MPO) produces highly reactive ROS during the neutrophils respiratory burst. Increased systemic levels of hydrogen peroxide (H2O2) in Ag have been associated with melanotic encapsulation-mediated refractoriness to Plasmodium [Kumar et al. 2003]. Heme-containing peroxidases (HPX) like MPO use H2O2 as an electron acceptor to catalyze a number of oxidative reactions. Five highly similar members of this family are found in vertebrates, which are most homologous to the Dm haemocyte peroxidasin and its mosquito orthologues, AgHPX4 and AaHPX4, suggesting that this subgroup expanded in vertebrates after their divergence from insects. Dual oxidases (DUOX) represent another group of vertebrate HPXs that combine a peroxidase with a NADPH-oxidase domain. These enzymes are expressed in various epithelia and are though to participate in local defense responses [Donko et al. 2005]. DUOX orthologs are present in Dm and mosquitoes. DmDuox silencing markedly increases the mortality rate of adult flies feeding on microbe-contaminated food [Ha et al. 2005]. The apoptotic response of Ag midgut cells to Plasmodium invasion involves peroxidase-mediated nitration, possibly associated with induced levels of AgDUOX [Kumar et al. 2004]. The HPX family has greatly expanded in insects producing seven orthologous groups. A double peroxidase (DBLPX) is present in insects with two highly divergent N-terminal (DBLPX-N) and C-terminal (DBLPX-C) peroxidase domains. Each domain type has one-to-one orthologs in the different insect species. Most peroxidases have 1:1 orthologues, but species-specific expansions have taken place in mosquitoes. ROS generated during the immune response are also potentially toxic to the host; it is therefore important that they be kept localized and rapidly neutralized. The thioredoxin and glutathione systems are important for protection against oxidative stress by reducing peroxides such as H2O2 to harmless products. The Dm and Ag genomes lack a glutathione reductase gene (GR) [Zdobnov et al. 2002], and functional studies indicated that glutathione is reactivated by Thioredoxin [Kanzok et al. 2001]. GR is also absent from Aa, suggesting that insects may only use the thioredoxin system. Surprisingly, genes with sequence homology to classic glutathione peroxidases (GPXs) are present in insects; two in Dm and three in mosquitoes. However, recent functional studies in Dm demonstrated that at least one (Gtpx-1) of the two fly homologues also uses thioredoxin as a substrate and is responsible for increased resistance to paraquat-induced oxidative stress [Missirlis et al. 2003]. Orthologues of Gtpx-1 and a second Dm GPX homologue (GPXH) are also present in Ag and Aa and are likely to use thioredoxin as a substrate. A third mosquito-specific GPX is probably catalytically inactive. Other enzymes such as superoxide dismutases (SODs), thioredoxin peroxidases (TPXs), peroxiredoxins (PRXs) and catalases (CATs) are involved in ROS detoxification.