(S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa 英文参考文献.docVIP
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(S)-α-Chlorohydrin Inhibits Protein Tyrosine Phosphorylation through Blocking Cyclic AMP - Protein Kinase A Pathway in Spermatozoa 英文参考文献
(S)-a-ChlorohydrinInhibitsProteinTyrosine
PhosphorylationthroughBlockingCyclicAMP-Protein
KinaseAPathwayinSpermatozoa
HaoZhang1.,HuanYu2.,XiaWang1.,WeiweiZheng1,BeiYang3,4,JingboPi3,GengshengHe1*,
WeidongQu1*
1KeyLaboratory ofthePublicHealthSafety,MinistryofEducation,DepartmentofEnvironmentalHealth,School ofPublicHealth,FudanUniversity,Shanghai,China,
2NeurologyDepartmentofHuashanHospital,FudanUniversity,Shanghai,China,3InstitutesforChemicalSafetySciences,TheHamnerInstitutesforHealthSciences,
ResearchTrianglePark,NorthCarolina,UnitedStatesofAmerica,4DepartmentofHistologyandEmbryology,BasicMedicalCollege,ChinaMedicalUniversity,Shenyang,
China
Abstract
a-Chlorohydrinisacommoncontaminantinfood.Its(S)-isomer,(S)-a-chlorohydrin(SACH),isknownforcausinginfertilityin
animalsbyinhibitingglycolysisofspermatozoa.TheaimofpresentworkwastoexaminetherelationshipbetweenSACH
andproteintyrosinephosphorylation(PTP),whichplaysacriticalroleinregulatingmammalianspermcapacitation.Invitro
exposure of SACH 50mM to isolated rat epididymal sperm inhibited PTP. Sperm-specific glyceraldehyde 3-phosphate
dehydrogenase (GAPDS) activities, the intracellular adenosine 59-triphosphate (ATP) levels, 39-59-cyclic adenosine
monophosphate (cAMP) levels and phosphorylation of protein kinase A (PKA) substrates in rat sperm were diminished
dramatically,indicatingthatbothglycolysisandthecAMP/PKAsignalingpathwaywereimpairedbySACH.Theinhibitionof
bothPTPandphosphorylationofPKAsubstratesbySACHcouldberestoredbyadditionofcAMPanalogdibutyryl-cAMP
(dbcAMP) and phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (IBMX). Moreover, addition of glycerol protected
glycolysis,ATPlevels,phosphorylationofPKAsubstratesandPTPagainsttheinfluenceofSACH.Theseresultssuggested
SACH inhibited PTP through blocking cAMP/PKA pathway in sperm, and PTP inhibition may play a role in infertility
associatedwithSACH.
Citation:ZhangH,YuH,WangX,ZhengW,YangB,etal.(2012)(S)-a-ChlorohydrinInhibitsProteinTyrosinePhosphorylationth
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