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NecroX‐5 suppresses sodium nitroprusside‐induced cardiac cell death through inhibition of JNK and caspase‐3 activation
Author(s) -
Lee Sung Ryul,
Lee Seon Joong,
Kim Soon Ha,
Ko Kyung Soo,
Rhee Byoung Doo,
Xu Zhelong,
Kim Nari,
Han Jin
Publication year - 2014
Publication title -
cell biology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.932
H-Index - 77
eISSN - 1095-8355
pISSN - 1065-6995
DOI - 10.1002/cbin.10242
Subject(s) - sodium nitroprusside , downregulation and upregulation , programmed cell death , apoptosis , snp , caspase 3 , caspase , cardiotoxicity , microbiology and biotechnology , kinase , protein kinase a , chemistry , pharmacology , toxicity , biology , medicine , nitric oxide , biochemistry , single nucleotide polymorphism , endocrinology , genotype , gene
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 NH 2 ‐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.