Connexin43 and AMPK Have Essential Role in Resistance to Oxidative Stress Induced Necrosis

Reactive oxygen species (ROS) induced oxidative stress leads to cell damage and neurological disorders in astrocytes. The gap junction protein connexin43 (Cx43) could form intercellular channels in astrocytes and the expression of Cx43 plays an important role in protecting the cells from damage. In the present study, we investigated the contribution of Cx43 to astrocytic necrosis induced by the ROS hydrogen peroxide (H₂O₂) and the mechanism by which AMPK was involved in this process. Fluorescence microscopy, flow cytometry, and western blot were used quantitatively and qualitatively to determine the cell apoptosis, necrosis, and protein expression. Lack of Cx43 expression or blockage of Cx43 channels resulted in increased H₂O₂-induced astrocytic necrosis, supporting a cell protective effect of functional Cx43 channels. Our data suggest that AMPK is important for Cx43-mediated ROS resistance. Inhibition of AMPK activation results in reduction of necrosis and ROS production. Taken together, our findings suggest that the role of Cx43 in response to H₂O₂ stress is dependent on the activation of AMPK signaling pathways and regulates ROS production and cell necrosis.