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Protective effect of KR-31378 on oxidative stress in cardiac myocytes

Authors
Kim, MY; Lee, S; Yi, KY; Yoo, SE; Lee, DH; Lim, H; Kim, HS; Lee, SH; Baik, EJ; Moon, CH; Jung, YS
Citation
Archives of pharmacal research, 28(12):1358-1364, 2005
Journal Title
Archives of pharmacal research
ISSN
0253-6269
Abstract
In this study, we investigated whether a novel anti-ischemic KATP opener KR-31378 [(2S,3S,4R)-N"-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methly-2-dimethoxymethly-2H-benzopyran-4-yl)-N'-benzylguanidine] has protective effect against oxidative stress-induced death in heart-derived H9c2 cells. Cell death was induced by BSO, butionine sulfoximine, which inhibits GSH synthesis and subsequently increases reactive oxygen species (ROS) level. Cell death was quantitatively determined by measuring lactate dehydrogenase (LDH) activity and stained by Hoechst 33258. BSO-induced ROS production and mitochondrial membrane potential (MMP) were measured using 2',7'-dichlorofluorescein diacetate oxidation and rhodamine 123, respectively. Both the LDH release and the ROS elevation induced by treatment of H9c2 cells with 10 mM BSO, were significantly decreased by KR-31378. These protective effect and antioxidant effect of KR-31378 appeared to be independent on KATP channel opening. Cells exposed to BSO showed an early reduction in MMP, and this reduction in MMP was significantly reversed by treatment with KR-31378. Caspase-3 activity in BSO treated H9c2 cells was remarkably increased, and this increased caspase-3 activity was significantly reversed by KR-31378. In conclusion, our results suggest that KR-31378 can produce cardioprotective effect against oxidative stress-induced cell death through antioxidant mechanism.
MeSH terms
AnimalsApoptosis/drug effectsBenzimidazoles/chemistryBenzimidazoles/diagnostic useButhionine Sulfoximine/antagonists & inhibitorsButhionine Sulfoximine/toxicityCaspase 3Caspases/antagonists & inhibitorsCaspases/metabolismCell LineDecanoic Acids/pharmacologyDose-Response Relationship, DrugFluoresceins/chemistryFluoresceins/diagnostic useGuanidines/pharmacology*Hydroxy Acids/pharmacologyL-Lactate Dehydrogenase/antagonists & inhibitorsL-Lactate Dehydrogenase/secretionMembrane Potentials/drug effectsMicroscopy, FluorescenceMitochondrial Membranes/drug effectsMitochondrial Membranes/physiologyMyocytes, Cardiac/cytologyMyocytes, Cardiac/drug effects*Myocytes, Cardiac/metabolismOxidative Stress/drug effects*Potassium Channel Blockers/pharmacologyPyrans/pharmacology*Reactive Oxygen Species/metabolismSulfonamides/pharmacologyThiourea/analogs & derivativesThiourea/pharmacologyTime Factors
PMID
16392669
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Physiology
AJOU Authors
이, 수환백, 은주문, 창현정, 이숙
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