Effect of Iron Overload and Iron Deficiency on Liver Hemojuvelin Protein 英文参考文献.docVIP

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Effect of Iron Overload and Iron Deficiency on Liver Hemojuvelin Protein 英文参考文献.doc

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Effect of Iron Overload and Iron Deficiency on Liver Hemojuvelin Protein 英文参考文献

EffectofIronOverloadandIronDeficiencyonLiver HemojuvelinProtein JanKrijt*,JanaFry′dlova′,LenkaKukacˇkova′,YuzoFujikura,PetrPrˇikryl,MartinVokurka,EmanuelNecˇas InstituteofPathophysiology,CharlesUniversityinPrague,FirstFacultyofMedicine,Prague,CzechRepublic Abstract Introduction: Hemojuvelin (Hjv) is a key component of the signaling cascade that regulates liver hepcidin (Hamp) expression.ThepurposeofthisstudywastodetermineHjvproteinlevelsinmiceandratssubjectedtoironoverloadand irondeficiency. Methods:C57BL/6micewereinjectedwithiron(200mg/kg);irondeficiencywasinducedbyfeedingofaniron-deficient diet,orbyrepeatedphlebotomies.Erythropoietin(EPO)-treatedmicewereadministeredrecombinantEPOat50U/mouse. Wistar rats were injected with iron (1200mg/kg), or fed an iron-deficient diet. Hjv protein was determined by immunoblotting, liver samples from Hjv2/2 mice were used as negative controls. Mouse plasma Hjv content was determinedbyacommercialELISAkit. Results: Liver crude membrane fraction from both mice and rats displayed a major Hjv-specific band at 35kDa, and a weakerbandof20kDa.Inmice,theintensityofthesebandswasnotchangedfollowingironinjection,repeatedbleeding, lowirondietorEPOadministration.NochangeinlivercrudemembraneHjvproteinwasobservediniron-treatedoriron- deficientrats.ELISAassayformouseplasmaHjvdidnotshowsignificantdifferencebetweenHjv+/+andHjv2/2mice.Liver Hamp mRNA, Bmp6 mRNA and Id1 mRNA displayed the expected response to iron overload and iron deficiency. EPO treatment decreased Id1 mRNA, suggesting possible participation of the bone morphogenetic protein pathway in EPO- mediateddownregulationofHampmRNA. Discussion:SincenodifferencesbetweenHjvproteinlevelswerefoundfollowingvariousexperimentalmanipulationsof bodyironstatus,theresultsindicatethat,invivo,substantialchangesinHampmRNAcanoccurwithoutnoticeablechanges ofmembranehemojuvelincontent.Therefore,modulationofhemojuvelinproteincontentapparentlydoesnotrepresent thelimitingstepinthecontrolofHampgeneexpression.