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The Pharmaceutical Society of Korea (대한약학회)
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Protective Effect of KR-31378 on Oxidative Stress in Cardiac Myocytes

  • Kim Mi-Young (Department of Physiology, School of Medicine, Ajou University) ;
  • Lee Sunkyung (Medical Science Division, Korea Research Institute of Chemical Technology) ;
  • Yi Kyu Yang (Medical Science Division, Korea Research Institute of Chemical Technology) ;
  • Yoo Sung Eun (Medical Science Division, Korea Research Institute of Chemical Technology) ;
  • Lee Dong-Ha (AgroPharma Research Institute, Dongbu Hannong Chemical Co. Ltd.) ;
  • Lim Hong (AgroPharma Research Institute, Dongbu Hannong Chemical Co. Ltd.) ;
  • Kim Ho Soon (AgroPharma Research Institute, Dongbu Hannong Chemical Co. Ltd.) ;
  • Lee Soo Hwan (Department of Physiology, School of Medicine, Ajou University) ;
  • Baik Eun Joo (Department of Physiology, School of Medicine, Ajou University) ;
  • Moon Chang-Hyun (Department of Physiology, School of Medicine, Ajou University) ;
  • Jung Yi-Sook (Department of Physiology, School of Medicine, Ajou University)
  • Published : 2005.12.01
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Abstract

In this study, we investigated whether a novel anti-ischemic $K_{ATP}$ 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 $K_{ATP}$ 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.

Keywords

References

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