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NADPH oxidase‐derived superoxide Anion‐induced apoptosis is mediated via the JNK‐dependent activation of NF‐κB in cardiomyocytes exposed to high glucose
Author(s) -
Tsai KunHsi,
Wang WeiJan,
Lin ChengWen,
Pai Peiying,
Lai TungYuan,
Tsai ChenYen,
Kuo WeiWen
Publication year - 2012
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.22847
Subject(s) - apocynin , nadph oxidase , p38 mitogen activated protein kinases , reactive oxygen species , superoxide , apoptosis , chemistry , kinase , microbiology and biotechnology , small interfering rna , glucose oxidase , phosphorylation , signal transduction , protein kinase a , biochemistry , biology , transfection , enzyme , gene
Hyperglycemia‐induced generation of reactive oxygen species (ROS) can lead to cardiomyocyte apoptosis and cardiac dysfunction. However, the mechanism by which high glucose causes cardiomyocyte apoptosis is not clear. In this study, we investigated the signaling pathways involved in NADPH oxidase‐derived ROS‐induced apoptosis in cardiomyocytes under hyperglycemic conditions. H9c2 cells were treated with 5.5 or 33 mM glucose for 36 h. We found that 33 mM glucose resulted in a time‐dependent increase in ROS generation as well as a time‐dependent increase in protein expression of p22 phox , p47 phox , gp91 phox , phosphorylated IκB, c‐Jun N‐terminal kinase (JNK) and p38, as well as the nuclear translocation of NF‐kB. Treatment with apocynin or diphenylene iodonium (DPI), NADPH oxidase inhibitors, resulted in reduced expression of p22 phox , p47 phox , gp91 phox , phosphorylated IκB, c‐Jun N‐terminal kinase (JNK) and p38. In addition, treatment with JNK and NF‐kB siRNAs blocked the activity of caspase‐3. Furthermore, treatment with JNK, but not p38, siRNA inhibited the glucose‐induced activation of NF‐κB. Similar results were obtained in neonatal cardiomyocytes exposed to high glucose concentrations. Therefore, we propose that NADPH oxidase‐derived ROS‐induced apoptosis is mediated via the JNK‐dependent activation of NF‐κB in cardiomyocytes exposed to high glucose. J. Cell. Physiol. 227: 1347–1357, 2012. © 2011 Wiley Periodicals, Inc.