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

Abstract

Purpose: In this study, we sought to test the hypothesis that oxidative stress injury in ischemic brains and H₂O₂-treated mouse neuroblastoma Neuro-2a cells (N2a) was related to STAT3 activation.

Materials and methods: Rat middle cerebral artery occlusion (MCAO) model and H₂O₂-treated mouse neuroblastoma Neuro-2a cells (N2a) were used to investigate the relationship between oxidative stress injury and STAT3 activation.

Results: 8-Hydroxy-2′-deoxyguanosine (8-OHdG) content and STAT3 protein phosphorylation level were significantly increased after cerebral ischemia-reperfusion. H₂O₂ 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 H₂O₂-induced injury in vitro, and JAK2 siRNA also alleviated H₂O₂-induced injury in N2a cell.

Conclusions: 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.

Keywords:

• Middle cerebral artery occlusion (MCAO)
• H₂O₂
• mouse neuroblastoma Neuro-2a (N2a) cells
• AG490
• signal transducer and activator of transcription 3 (STAT3)

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the grants from National Natural Science Foundation of China (81373003 and 81874262).