JAK2/STAT3 involves oxidative stress-induced cell injury in N2a cells and a rat MCAO model.

In this study, we sought to test the hypothesis that oxidative stress injury in ischemic brains and HO-treated mouse neuroblastoma Neuro-2a cells (N2a) was related to STAT3 activation. Rat middle cerebral artery occlusion (MCAO) model and HO-treated mouse neuroblastoma Neuro-2a cells (N2a) were used to investigate the relationship between oxidative stress injury and STAT3 activation. 8-Hydroxy-2'-deoxyguanosine (8-OHdG) content and STAT3 protein phosphorylation level were significantly increased after cerebral ischemia-reperfusion. HO treatment inhibited the cell viability, induced the apoptosis, and further raised pSTAT3 protein level in N2a cells. Moreover, the addition of AG490, the protein inhibitor of JAK2, significantly alleviated cerebral ischemic damage in vivo and HO-induced injury , and JAK2 siRNA also alleviated HO-induced injury in N2a cell. JAK2/STAT3 pathway may play a crucial role in mediating reactive oxidative species (ROS)-induced cell injury in rat middle cerebral artery occlusion (MCAO) model and N2a cells. ROS scavenging and down-regulation of STAT3 activation might be a candidate design of therapeutic strategies against oxidative stress-related neurological diseases.