Department of Pharmacy, University of Salerno, 84084 Fisciano, Italy.
Int J Mol Sci. 2021 Oct 27;22(21):11599. doi: 10.3390/ijms222111599.
Hypoxia is the leading cause of death in cardiomyocytes. Cells respond to oxygen deprivation by activating cytoprotective programs, such as mitochondrial connexin43 (mCx43) overexpression and the opening of mitochondrial K channels, aimed to reduce mitochondrial dysfunction. In this study we used an in vitro model of CoCl-induced hypoxia to demonstrate that mCx43 and K channels cooperate to induce cytoprotection. CoCl administration induces apoptosis in H9c2 cells by increasing mitochondrial ROS production, intracellular and mitochondrial calcium overload and by inducing mitochondrial membrane depolarization. Diazoxide, an opener of K channels, reduces all these deleterious effects of CoCl only in the presence of mCx43. In fact, our results demonstrate that in the presence of radicicol, an inhibitor of Cx43 translocation to mitochondria, the cytoprotective effects of diazoxide disappear. In conclusion, these data confirm that there exists a close functional link between mCx43 and K channels.
缺氧是心肌细胞死亡的主要原因。细胞通过激活细胞保护程序来应对缺氧，例如线粒体连接蛋白 43（mCx43）过表达和线粒体 K 通道的开放，旨在减少线粒体功能障碍。在这项研究中，我们使用 CoCl 诱导的缺氧体外模型证明 mCx43 和 K 通道合作诱导细胞保护。CoCl 处理通过增加线粒体 ROS 产生、细胞内和线粒体钙超载以及诱导线粒体膜去极化来诱导 H9c2 细胞凋亡。二氮嗪，一种 K 通道开放剂，仅在存在 mCx43 的情况下减少 CoCl 的所有这些有害作用。事实上，我们的结果表明，在 Cx43 易位到线粒体的抑制剂 Radicicol 存在的情况下，二氮嗪的细胞保护作用消失。总之，这些数据证实了 mCx43 和 K 通道之间存在密切的功能联系。
