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Novel Lactam Type Pyridine Derivatives Improves Myocardium Dysfunction Derived from Ischemic Injury

Authors
 Kyung-Eun Kim  ;  Heesang Song  ;  Minji Cha  ;  Byeong-Wook Song  ;  Eunju Choi  ;  Onju Ham  ;  Chang Yeon Lee  ;  Seong Yong Choi  ;  Se-Yeon Lee  ;  Yangsoo Jang  ;  Ki-Chul Hwang 
Citation
 TISSUE ENGINEERING AND REGENERATIVE MEDICINE, Vol.6(13) : 1191-1197, 2009 
Journal Title
 TISSUE ENGINEERING AND REGENERATIVE MEDICINE 
ISSN
 1738-2696 
Issue Date
2009
Keywords
cardiomyocyte ; lactam pyridine derivative ; ischemia ; apoptosis
Abstract
The extended acute myocardial ischemia (AMI) results in cardiac myocytes death. In the present study, we show that lactam pyridine derivative, SK-D80375, have the effects on cell survival in hypoxic cardiomyocytes and might be used as an anti-ischemic drug. The lactam pyridine derivatives are inhibitors of the late sodium current, which decreases sodium-dependent intracellular calcium overload in ischemia/reperfusion-injured hearts. We found that pretreatment with SK-D80375 significantly decreased the level of intracellular Ca2+ and the expression level of the Na+-Ca2+ exchanger by 39±2.5% and 19±0.5%, respectively in hypoxic cardiomyocytes compared to untreated controls. In addition, the expression level of sarcoplasmic reticulum Ca2+ ATPase 2a was significantly increased by 37±1.5% in SK-D80375-treated hypoxic cardiomyocytes compared to untreated controls. The induction of Hsp70 was observed in SK-D80375-treated hypoxic cardiomyocytes with dose-dependent manner and the highest level of Hsp70 was induced at the concentration of 2.5 μM SK-D80375. The echocardiographic analysis showed that heart function was significantly improved in SK-D80375-injected ischemic hearts. These results demonstrate that lactam pyridine derivative, SK-D80375, have beneficial effects on hypoxia-induced cell death, therefore, might be used as a novel anti-ischemia drug
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Appears in Collections:
1. College of Medicine (의과대학) > Yonsei Biomedical Research Center (연세의생명연구원) > 1. Journal Papers
1. College of Medicine (의과대학) > BioMedical Science Institute (의생명과학부) > 1. Journal Papers
1. College of Medicine (의과대학) > Medical Research Center (임상의학연구센터) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Song, Byeong Wook(송병욱)
Lee, Se Yeon(이세연)
Jang, Yang Soo(장양수) ORCID logo https://orcid.org/0000-0002-2169-3112
Cha, Min Ji(차민지)
Choi, Eun Ju(최은주)
Ham, On Ju(함온주)
Hwang, Ki Chul(황기철)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/105610
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