Redox balance mechanisms in Schistosoma mansoni rely on peroxiredoxins and albumin and implicate peroxiredoxins as novel drug targets.

摘要: Schistosoma mansoni, a causative agent of schistosomiasis, resides in the hepatic portal circulation their human host up to 30 years without being eliminated by immune attack. Production an antioxidant "firewall," which would neutralize oxidative assault generated defenses, is one proposed survival mechanism parasite. Schistosomes lack catalase, main H2O2-neutralizing enzyme many organisms, and glutathione peroxidases are phospholipid class with poor reactivity toward H2O2. Evidence implicates peroxiredoxins (Prx) as providing enzymatic activity reduce H2O2 Quantitative monitoring Prx mRNAs during parasite life cycle indicated that proteins differentially expressed, highest expression occurring adult stages (oxidative resistant stages). Incubation schistosomula Prx1 double-stranded RNA knocked down total resulted lowered cultured parasites compared controls demonstrating essential proteins. These results represent first report lethal gene silencing Schistosoma. Investigation downstream effects revealed abrupt increase lipid peroxides generation several oxidized Using mass spectrometry, albumin actin were identified Gene analysis showed schistosome was induced stress. This study highlights potential new targets for anti-schistosome drug development novel, sacrificial oxidant scavenging protein redox regulation.