Protective Antioxidant and Antiapoptotic Effects of ZnCl2 in Rat Pancreatic Islets Cultured in Low and High Glucose Concentrations 英文参考文献.docVIP

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Protective Antioxidant and Antiapoptotic Effects of ZnCl2 in Rat Pancreatic Islets Cultured in Low and High Glucose Concentrations 英文参考文献.doc

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Protective Antioxidant and Antiapoptotic Effects of ZnCl2 in Rat Pancreatic Islets Cultured in Low and High Glucose Concentrations 英文参考文献

ProtectiveAntioxidantandAntiapoptoticEffectsofZnCl2 inRatPancreaticIsletsCulturedinLowandHighGlucose Concentrations JessicaDuprez,LeticiaP.Roma,Anne-Franc?oise Close,Jean-ChristopheJonas* Universite′ CatholiquedeLouvain,InstitutdeRechercheExpe′rimentaleetClinique,Po?led’Endocrinologie,Diabe`te etNutrition,Brussels,Belgium Abstract Aim/Hypothesis:Ratpancreaticisletcellapoptosisisminimalafterprolongedculturein10mmol/lglucose(G10),largely increased in 5mmol/l glucose (G5) and moderately increased in 30mmol/l glucose (G30). This glucose-dependent asymmetric V-shaped profile is preceded by parallel changes in the mRNA levels of oxidative stress-response genes like Metallothionein1a(Mt1a).Inthisstudy,wetestedtheeffectofZnCl2,apotentinducerofMt1a,onapoptosis,mitochondrial oxidativestressandalterationsofglucose-inducedinsulinsecretion(GSIS)inducedbyprolongedexposuretolowandhigh ermediateglucoseconcentrations. Methods: Male Wistar rat islets were cultured in RPMI medium. Islet gene mRNA levels were measured by RTq-PCR. Apoptosis was quantified by measuring islet cytosolic histone-associated DNA fragments and the percentage of TUNEL- positive b-cells. Mitochondrial thiol oxidation was measured in rat islet cell clusters expressing ‘‘redox sensitive GFP’’ targetedtothemitochondria(mt-roGFP1).InsulinsecretionwasmeasuredbyRIA. Results:AsobservedforMt1amRNAlevels,b-cellapoptosisandlossofGSIS,cultureineitherG5orG30vs.G10significantly increasedmt-roGFP1oxidation.WhileTPENdecreasedMt1a/2amRNAinductionbyG5,additionof50–100mMZnCl2tothe culturemediumstronglyincreasedMt1a/2amRNAandproteinlevels,reducedearlymt-roGFPoxidationandsignificantly decreasedlateb-cellapoptosisafterprolongedcultureinG5orG30vs.G10.Itdidnot,however,preventthelossofGSIS underthesecultureconditions. Conclusion:ZnCl2reducesmitochondrialoxidativestressandimprovesratb-cellsurvivalduringcultureinthepresenceof ermediateglucoseconcentrationswithoutimprovingtheiracuteGSIS. Citation:DuprezJ,RomaLP,CloseA-F,JonasJ-C