Prostatic Acid Phosphatase Is Required for the Antinociceptive Effects of Thiamine and Benfotiamine 英文参考文献.docVIP

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Prostatic Acid Phosphatase Is Required for the Antinociceptive Effects of Thiamine and Benfotiamine 英文参考文献.doc

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Prostatic Acid Phosphatase Is Required for the Antinociceptive Effects of Thiamine and Benfotiamine 英文参考文献

ProstaticAcidPhosphataseIsRequiredforthe AntinociceptiveEffectsofThiamineandBenfotiamine JulieK.Hurt1,JenniferL.Coleman1,BrendanJ.Fitzpatrick1,BonnieTaylor-Blake1,ArleneS.Bridges1, PirkkoVihko2,MarkJ.Zylka1* 1DepartmentofCellandMolecularPhysiology,UNCNeuroscienceCenter,UniversityofNorthCarolinaatChapelHill,ChapelHill,UnitedStatesofAmerica,2Department ofClinicalMedicine,DivisionofClinicalChemistry,HUSLAB,UniversityofHelsinki,Helsinki,Finland Abstract Thiamine(VitaminB1)isanessentialvitaminthatmustbeobtainedfromthedietforproperneurologicalfunction.Athigher doses, thiamine and benfotiamine (S-benzoylthiamine O-monophosphate, BT)–a phosphorylated derivative of thiamine– haveantinociceptive effectsin animalsandhumans,although howthese compounds inhibitpain is unknown.Here, we foundthatProstaticacidphosphatase(PAP,ACPP)candephosphorylateBTinvitro,indorsalrootganglia(DRG)neurons andinprimary-afferentaxonterminalsinthedorsalspinalcord.ThedephosphorylatedproductS-benzoylthiamine(S-BT) then decomposes to O-benzoylthiamine (O-BT) and to thiamine in a pH-dependent manner, independent of additional enzymes.ThisuniquereactionmechanismrevealsthatBTonlyrequiresaphosphataseforconversiontothiamine.However, we found that the antinociceptive effects of BT, thiamine monophosphate (TMP) and thiamine–a compound that is not phosphorylated–wereentirelydependentonPAPatthespinallevel.Moreover,pharmacokineticstudieswithwild-typeand Pap2/2 mice revealed that PAP is not required for the conversion of BT to thiamine invivo. Taken together, our study highlightsanobligatoryroleforPAPintheantinociceptiveeffectsofthiamineandphosphorylatedthiamineanalogs,and suggestsanovelphosphatase-independentfunctionforPAP. Citation:HurtJK,ColemanJL,FitzpatrickBJ,Taylor-BlakeB,BridgesAS,etal.(2012)ProstaticAcidPhosphataseIsRequiredfortheAntinociceptiveEffectsof ThiamineandBenfotiamine.PLoSONE7(10):e48562.doi:10.1371/journal.pone.0048562 Editor:AlexanderBinshtok,TheHebrewUniversityMedicalSchool,Israel ReceivedAu