Paradoxical effects of ginkgolide B on cardiomyocyte contractile function in normal and high-glucose

来源 :Acta Pharmacologica Sinica | 被引量 : 0次 | 上传用户:woaiyueyue1314
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Aim:Ginkgo biloba extract is a natural product used widely for cerebral andcardiovascular diseases.It is mainly composed of terpene lactones (ginkgolide Aand B) and flavone glycosides (eg quercetin and kaempferol).To better under-stand the cardiac electromechanical action of Ginkgo biloba extract in normal anddiabetic states,this study was designed to examine the effect of ginkgolide B oncardiomyocyte contractile function under normal and high-glucose environments.Methods:Isolated adult rat ventricular myocytes were cultured for 6h in a serum-free medium containing either normal (NG;5.5mmol/L) or high (HG;25.5mmol/L)glucose with or without ginkgolide B (0.5-2.0μg/mL).Mechanical propertieswere evaluated using the IonOptix MyoCam system.Contractile properties ana-lyzed included peak shortening (PS),maximal velocity of shortening/relengthening(±dl/dt),time-to-PS (TPS) and time-to-90% relengthening (TR_(90)).Levels of essen-tial Ca~(2+) regulatory proteins sarco(endo)plasmic reticulum Ca~(2+)-ATPase (SERCA2a),phospholamban (PLB) and Na~+-Ca~(2+) exchanger (NCX) were assessed by Westernblotting.Results:Ginkgolide B nullified HG-induced prolongation in TR_(90).However,ginkgolide B depressed PS,±dl/dt and shortened TPS in NG and HGcells.Ginkgolide B also prolonged TR_(90) in NG cells.Western blot analysis re-vealed that HG upregulated SERCA2a and downregulated PLB expression with-out affecting that of NCX.Ginkgolide B disrupted the NG-HG response pattern inSERCA2a and NCX without affecting that of PLB.Conclusion:Ginkgolide Baffects cardiomyocyte contractile function under NG or HG environments in aparadoxical manner,which may be attributed to uneven action on Ca~(2+) regulatoryproteins under NG and HG conditions. Aim:Ginkgo biloba extract is a natural product used widely for cerebral andcardiovascular diseases.It is mainly composed of terpene lactones (ginkgolide Aand B) and flavone glycosides (eg quercetin and kaempferol).To better under- stand the cardiac electromechanical action of Ginkgo biloba Extract in normal and diabetic states,this study was designed to examine the effect of ginkgolide B oncardiomyocyte contractile function under normal and high-glucose environments.Methods:Isolated adult rat ventricular myocytes were cultured for 6h in a serum-free medium containing either normal (NG 5.5mmol/L) or high (HG; 25.5mmol/L)glucose with or without ginkgolide B (0.5-2.0μg/mL). Mechanical properties were evaluated using the IonOptix MyoCam system.Contractile properties ana-lyzed included peak shortening (PS ),maximal velocity of shortening/relengthening(±dl/dt),time-to-PS (TPS) and time-to-90% relengthening (TR_(90)).Levels of essen- tial Ca~(2+) regulatory Proteins sarco(endo)plasmic reticulum Ca ~2-(2+)-ATPase (SERCA2a), phospholamban (PLB) and Na~+-Ca~(2+) exchanger (NCX) were assessed by Western blotting. Results: Ginkgolide B nullified HG-induced prolongation in TR_(90). However, ginkgolide B depressed PS, ±dl/dt and shortened TPS in NG and HGcells.Ginkgolide B also prolonged TR_(90) in NG cells.Western blot analysis re-vealed that HG upregulated SERCA2a and downregulated PLB expression with-out affecting that Of NCX.Ginkgolide B disrupted the NG-HG response pattern in SERCA2a and NCX without affecting that of PLB.Conclusion: Ginkgolide Baffects cardiomyocyte contractile function under NG or HG environments in a paradoxical manner,which may be attributed to uneven action on Ca~(2+ ) regulatoryproteins under NG and HG conditions.
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