Involvement of JNK1/2-NF-κBp65 in the regulation of HMGB2 in myocardial ischemia/reperfusion-induced apoptosis in human AC16 cardiomyocytes.

Published on Oct 1, 2018in Biomedicine & Pharmacotherapy6.53
· DOI :10.1016/J.BIOPHA.2018.07.015
Wei Zhang2
Estimated H-index: 2
(Tongji University),
Yangyang Zhang2
Estimated H-index: 2
(Tongji University)
+ 4 AuthorsYawei Xu27
Estimated H-index: 27
(Tongji University)
Sources
Abstract
Abstract JNK1/2 and NF-κB signal are essential signaling pathways that mediate a variety of cellular processes, including cell survival, apoptosis, inflammation and angiogenesis. JNK1/2 activation and NF-κBp65 nuclear translocation have been found in ischemia/reperfusion (I/R)-induced injury. However, the regulation of JNK1/2-NF-κBp65 signaling pathway remains unclear. To examine the function and possible mechanism of HMGB2 in I/R-induced cell injury, human AC16 cardiomyocytes transfected with pLVX-Puro-HMGB2 were treated with SP600125 (JNK1/2 inhibitor) or PDTC (NF-κB inhibitor) and that following I/R injury were transfected with HMGB2-shRNA. The cell proliferation and apoptosis were measured by CCK-8, flow cytometry and TUNEL, respectively. The expression of HMGB2, Cleaved PARP and Caspase-3, Bax and Bcl-2 and activity of MAPKs and NF-κBp65 were measured by Western blot. Here, we found that I/R time-dependently induced the increase in the expression of HMGB2 in AC16 cardiomyocytes. HMGB2 silencing significantly inhibited I/R-induced the cell proliferation reduction, cell apoptosis, activation of ERK1/2, JNK1/2 and NF-κBp65, increased Bax, Cleaved PARP and Caspase-3 and decreased Bcl-2 expression. HMBG2 overexpression mimicked the effect of I/R-induced injury in AC16 cardiomyocytes, which was reversed by treatment with SP600125 or PDTC. Moreover, PDTC treatment in rats following I/R injury also showed decreases in the cell apoptosis, HMGB2, Cleaved PARP and Caspase-3 and Bax expression, and JNK1/2 activation. Taken together, our findings suggest that HMBG2 overexpression promotes I/R-induced cell apoptosis through activating the JNK1/2-NF-κBp65 signaling in AC16 cardiomyocytes.
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