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.


METHODS
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.
Department of Neurology, the Fourth Hospital of Jinan, Affiliated Hospital of Taian Medical College, No. 30, Shifan Road, Jinan, 250021, China.
Haiying
H
Zhu
Haiyan
H
Zhu
Shuping
S
Xiao
Hongyu
H
Sun
Chunli
C
Xie
Yingwen
Y
Ma
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000473:pathology; D053454:Caspase 12 / Q000378:metabolism; D003342:Corpus Striatum / Q000473:pathology / Q000503:physiopathology; D004721:Endoplasmic Reticulum / Q000473:pathology / Q000502:physiology*; D005625:Frontal Lobe / Q000473:pathology / Q000503:physiopathology; D007091:Image Processing, Computer-Assisted; D048670:MAP Kinase Kinase 4 / Q000502:physiology*; D008297:Male; D008856:Microscopy, Fluorescence; D010296:Parietal Lobe / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000473:pathology / Q000503:physiopathology*; D051742:Transcription Factor CHOP / Q000378:metabolism
C497249:DDIT3 protein, human; D051742:Transcription Factor CHOP; D048670:MAP Kinase Kinase 4; C506443:Casp12 protein, rat; D053454:Caspase 12