Dramatic Increase in Glycerol Biosynthesis upon Oxidative Stress in the Anaerobic Protozoan Parasite Entamoeba histolytica 英文参考文献.docVIP

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Dramatic Increase in Glycerol Biosynthesis upon Oxidative Stress in the Anaerobic Protozoan Parasite Entamoeba histolytica 英文参考文献.doc

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Dramatic Increase in Glycerol Biosynthesis upon Oxidative Stress in the Anaerobic Protozoan Parasite Entamoeba histolytica 英文参考文献

DramaticIncreaseinGlycerolBiosynthesisupon OxidativeStressintheAnaerobicProtozoanParasite Entamoebahistolytica AfzalHusain1,2¤,DanSato3,GhulamJeelani1,4,TomoyoshiSoga3,TomoyoshiNozaki1,5* 1Department of Parasitology, National Institute of Infectious Diseases, Tokyo, Japan, 2Department of Parasitology, Gunma University Graduate School of Medicine, Maebashi, Japan, 3Institute for Advanced Biosciences, Keio University, Tsuruoka, Japan, 4Department of Biochemistry and Integrative Medical Biology, School of Medicine,KeioUniversity,Tokyo,Japan,5GraduateSchoolofLifeandEnvironmentalSciences,UniversityofTsukuba,Tsukuba,Japan Abstract Entamoebahistolytica,amicroaerophilicentericprotozoanparasite,causesamebiccolitisandextraintestinalabscessesin millions of inhabitants of endemic areas. Trophozoites of E. histolytica are exposed to a variety of reactive oxygen and nitrogenspeciesduringinfection.SinceE.histolyticalackskeycomponentsofcanonicaleukaryoticanti-oxidativedefense systems,suchascatalaseandglutathionesystem,alternativenot-yet-identifiedanti-oxidativedefensestrategieshavebeen postulatedtobeoperatinginE.histolytica.Inthepresentstudy,weinvestigatedglobalmetabolicresponsesinE.histolytica inresponsetoH2O2-andparaquat-mediatedoxidativestressbymeasuringchargedmetabolitesoncapillaryelectrophoresis andtime-of-flightmassspectrometry.Wefoundthatoxidativestresscauseddrasticmodulationofmetabolitesinvolvedin glycolysis, chitin biosynthesis, and nucleotide and amino acid metabolism. Oxidative stress resulted in the inhibition of glycolysisasaresultofinactivationofseveralkeyenzymes,leadingtotheredirectionofmetabolicfluxtowardsglycerol production, chitin biosynthesis, and the non-oxidative branch of the pentose phosphate pathway. As a result of the repressionofglycolysisasevidencedbytheaccumulationofglycolyticintermediatesupstreamofpyruvate,andreduced ethanolproduction,thelevelsofnucleosidetriphosphatesweredecreased.Wealsoshowedforthefirsttimethepresence of functional glycerol biosynthet