Interaction between ROS and p38MAPK contributes to chemical hypoxia-induced injuries in PC12 cells.

The present study investigated whether there is an interaction between reactive oxygen species (ROS) and p38 mitogen-activated protein kinase (MAPK) during chemical hypoxia-induced injury in PC12 cells. The results of the present study showed that cobalt chloride (CoCl₂), a chemical hypoxia agent, markedly induced ROS generation and phosphorylation of p38MAPK, as well as neuronal injuries. N-acetylcysteine (NAC), a ROS scavenger, blocked CoCl₂-induced phosphorylation of p38MAPK. In addition, SB203580, an inhibitor of p38MAPK attenuated not only CoCl₂-induced activation of p38MAPK, but also ROS production. These results suggest that ROS and p38MAPK are capable of interacting positively during chemical hypoxia. Furthermore, NAC and SB203580 markedly prevented CoCl₂-induced cytotoxicity, apoptosis and a loss of mitochondrial membrane potential. Taken together, our findings suggest that the positive interaction between CoCl₂ induction of ROS and p38MAPK activation may play a significant role in CoCl₂-induced neuronal injuries. We provide new insights into the mechanisms responsible for CoCl₂-induced injuries in PC12 cells.