Activation and crosstalk between the endoplasmic reticulum road and JNK pathway in ischemia-reperfusion brain injury.

Background: Recent studies suggest that endoplasmic reticulum stress (ERS) is the key process in ischemic brain injury. The JNK pathway is also involved in the process of ischemic brain injury.

Method: We established a middle cerebral artery occlusion/reperfusion (MCAO/R) model in rats; detected the changes in c-Jun N-terminal kinase (JNK), GADD153 and caspase-12 at different reperfusion time points by immunohistochemistry, Western blot and double-label immunofluorescence; and observed the effect of JNK inhibitor SP600125 on the expression of JNK, GADD153 and caspase-12 to explore the relationship between the endoplasmic reticulum road and JNK pathway.

Results: The expression of the two hallmarks of ERS-GADD153 and caspase-12-significantly increased, and the activation of JNK also obviously increased. After interference by SP600125, the expression of p-JNk and caspase-12 obviously decreased, whereas the decrease of GADD153 occurred only after 24 h reperfusion.

Conclusions: Both ERS and JNK pathways are involved in the pathological process of ischemic brain injury. The JNK pathway may be involved in the process of ERS, but perhaps has more effect on the caspase-12 pathway.