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NecroX-5 suppresses sodium nitroprusside-induced cardiac cell death through inhibition of JNK and caspase-3 activation

Authors

  • Sung Ryul Lee,

    1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea
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  • Seon Joong Lee,

    1. Department of Health Sciences and Technology, Inje University, Busan, Republic of Korea
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  • Soon Ha Kim,

    1. Strategy and Development, LG Life Sciences Ltd, Seoul, Republic of Korea
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  • Kyung Soo Ko,

    1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea
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  • Byoung Doo Rhee,

    1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea
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  • Zhelong Xu,

    1. Department of Physiology & Pathophysiology, Medical University, Tianjin, People's Republic of China
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  • Nari Kim,

    1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea
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  • Jin Han

    Corresponding author
    1. National Research Laboratory for Mitochondrial Signaling, Department of Physiology, College of Medicine, Cardiovascular and Metabolic Disease Center, Inje University, Busan, Republic of Korea
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Abstract

Although sodium nitroprusside (SNP) is an effective hypotensive drug and is often used in pediatric intensive care units and to treat acute heart failure, clinical application of SNP is limited by its cardiotoxicity. NecroX-5 (NX-5) was recently developed and has the capacity to inhibit necrotic cell death. No current literature addresses whether NX-5 suppresses SNP-induced cell death or its mechanism of action. We have investigated the protective role of NX-5 against SNP-induced cell death in cardiomyocyte-like H9c2 cells. SNP treatment induced severe cell death, possibly through phosphorylation of stress-activated protein kinase/c-Jun NH2-terminal kinase (JNK) and activation of the apoptotic signaling pathway, including downregulation of Bcl-2 and cleavage of caspase-3. However, NX-5 suppresses SNP-induced cell death through inhibition of JNK activation and suppression of both downregulation of Bcl-2 protein expression and caspase-3 cleavage. These findings will provide insights and facilitate development of antidotes to SNP toxicity in cardiac cells.

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