Journal
JOURNAL OF CELLULAR PHYSIOLOGY
Volume 227, Issue 4, Pages 1347-1357Publisher
WILEY-BLACKWELL
DOI: 10.1002/jcp.22847
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Funding
- National Science Council of Republic of China [NSC99-2320-B-039-033-MY3, NSC 96-2320-B-039-035 MY3]
- Taiwan Department of Health Clinical Trial and Research Center of Excellence [DOH99-TD-B-111-004, DOH100-TD-B-111-004]
- Taiwan Department of Health Cancer Research Center of Excellence [DOH99-TD-C-111-005, DOH100-TD-C-111-005]
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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 p22phox, p47phox, gp91phox, phosphorylated I?B, 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 p22phox, p47phox, gp91phox, phosphorylated I?B, 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-?B. 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-B in cardiomyocytes exposed to high glucose. J. Cell. Physiol. 227: 1347-1357, 2012. (C) 2011 Wiley Periodicals, Inc.
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