Department of Cardiology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, P.R. China.
Mol Med Rep. 2018 Jan;17(1):729-734. doi: 10.3892/mmr.2017.7967. Epub 2017 Nov 6.
Cardiac connexin43 (Cx43) serves an essential role in maintaining the functional integrity of the heart. The present study investigated the effect of glucose deprivation (GD) on Cx43 protein expression levels in H9c2 cells, and demonstrated that following 2 h GD, Cx43 protein expression levels in H9c2 cells increased by ~68%. In addition, GD activated the extracellular signal‑regulated kinase (ERK)/mitogen‑activated protein kinase (MAPK) signaling pathway, which regulated the expression levels of cardiac Cx43. A MAPK inhibitor and U0126, an ERK inhibitor, abolished the effects of GD on Cx43 expression levels. Under GD, the protein expression levels of Beclin‑1, p62 and LC3 were augmented, and were decreased in the presence of ERK inhibitor or siRNA‑ERK. In addition, H9c2 cells exposed to GD exhibited marked increase in LDH release and decreased MTT reduction activity, all of which were not significantly reversed by U0126 treatment. Therefore, the ERK/MAPK signaling pathway may be involved in elevating cardiac Cx43 expression levels under GD in H9c2 cells.
心脏连接蛋白 43(Cx43)在维持心脏功能完整性方面起着至关重要的作用。本研究探讨了葡萄糖剥夺(GD)对 H9c2 细胞中 Cx43 蛋白表达水平的影响,结果表明,GD2h 后,H9c2 细胞中 Cx43 蛋白表达水平增加了约 68%。此外,GD 激活了细胞外信号调节激酶(ERK)/丝裂原活化蛋白激酶(MAPK)信号通路,调节心脏 Cx43 的表达水平。MAPK 抑制剂和 ERK 抑制剂 U0126 消除了 GD 对 Cx43 表达水平的影响。在 GD 条件下,Beclin-1、p62 和 LC3 的蛋白表达水平增加,而在 ERK 抑制剂或 siRNA-ERK 存在的情况下则减少。此外,暴露于 GD 的 H9c2 细胞中 LDH 释放明显增加,MTT 还原活性降低,但 U0126 处理并未显著逆转这些变化。因此,ERK/MAPK 信号通路可能参与了 GD 诱导的 H9c2 细胞中心脏 Cx43 表达水平的升高。