KR-31378 protects cardiac H9c2 cells from chemical hypoxia-induced cell death via inhibition of JNK/p38 MAPK activation.

Abstract

Using a metabolic inhibition buffer as an ischemic model, we show here that KR-31378, a cardioselective ATP-sensitive potassium channel opener, protects H9c2 cells from chemical hypoxia (CH)-induced cell death. Our previous study showed that CH downregulated caspase activities, but led to differential activation of mitogen-activated protein kinases (MAPKs) in H9c2 cells. The repression of CH-induced c-jun N-terminal kinase (JNK)/p38 MAPK activation resulted in partial protection against CH- induced cell death, implying JNK/p38 MAPK's causative role in CH-induced cell death. This study furthers that research and examines if KR-31378's protective effect came from modulating MAPK activity and/or caspase activity in H9c2 cells. Although KR-31378 did not restore downregulated caspase-3 activity, it did block the activation of JNK and p38 MAPK in a dose-dependent manner. Extracellular signal-regulated kinase activity was not recovered by KR-31378 treatment. CH-induced reactive oxygen species (ROS) generation was suppressed by KR-31378. Thus our results indicate that the cardioprotective effect of KR-31378 in CH is due, at least in part, to the differential inhibition of MAPKs.

• Authors: Yong-Sam Jung, Dong-Ha Lee, Hong Lim, Kyu Yang Yi, Sung-Eun Yoo, Eunhee Kim
• Journal: The Japanese journal of physiology (Jpn J Physiol) Vol. 54 Issue 6 Pg. 575-83 (Dec 2004) ISSN: 0021-521X [Print] Japan
• PMID: 15760490 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Anthracenes
• Butadienes
• Guanidines
• Imidazoles
• N''-cyano-N-(6-amino-3,4-dihydro-3-hydroxy-2-methyl-2-dimethoxymethyl-2H-benzopyran-4-yl)-N'-benzylguanidine
• Nitriles
• Pyrans
• Pyridines
• Reactive Oxygen Species
• U 0126
• pyrazolanthrone
• JNK Mitogen-Activated Protein Kinases
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4
• Mitogen-Activated Protein Kinase Kinases
• SB 203580

Topics

• Animals
• Anthracenes (pharmacology)
• Butadienes (pharmacology)
• Cell Death (drug effects, physiology)
• Cell Hypoxia (physiology)
• Cell Line
• Enzyme Activation (drug effects)
• Guanidines (chemistry, pharmacology)
• Imidazoles (pharmacology)
• JNK Mitogen-Activated Protein Kinases (antagonists & inhibitors)
• MAP Kinase Kinase 4
• Mitogen-Activated Protein Kinase Kinases (antagonists & inhibitors)
• Molecular Structure
• Myocardium (cytology)
• Nitriles (pharmacology)
• Pyrans (chemistry, pharmacology)
• Pyridines (pharmacology)
• Reactive Oxygen Species
• p38 Mitogen-Activated Protein Kinases (antagonists & inhibitors)