Regulation of JNK signaling pathway and RIPK3/AIF in necroptosis-mediated global cerebral ischemia/reperfusion injury in rats.

Regulation of JNK signaling pathway and RIPK3/AIF in necroptosis-mediated global cerebral ischemia/reperfusion injury in rats. Exp Neurol. 2020 Jun 02;:113374 Authors: Hu W, Wu X, Yu D, Zhao L, Zhu X, Li X, Huang T, Chu Z, Xu Y Abstract Receptor-interacting protein kinase 3 (RIPK3) regulates a newly discovered cell death form called necroptosis. RIPK3 nuclear translocation and inflammatory factor release are involved in necroptosis after rat global cerebral ischemia/reperfusion (I/R) injury. The purpose of this study was to investigate the effects of interactions between the RIPK3 and apoptosis-inducing factor (AIF) necroptosis pathway and the JNK-mediated inflammatory pathway. Rats were subjected to 4-vessel occlusion and reperfusion injury. RIPK3 inhibitor GSK872, RIPk3 recombinant adeno-associated virus (rAAV) and JNK-specific inhibitor SP600125 were intracerebroventricular injected before I/R. Hippocampus CA1 tissue were obtained and RIPK3, AIF, p-JNK, IL-6 were determined by western blot analysis. The RIPK3 and AIF interaction were also analyzed by immunofluorescence and immunoprecipitation. The expression of endogenous RIPK3, AIF, p-JNK and IL-6 was increased in hippocampus CA1 in I/R group. In addition, RIPK3 was increased in both the total protein and nuclear protein. GSK872 administration reduced the number of neuron deaths and the expression of RIPK3, p-JNK and IL-6. GSK872 also improve the rat neurobehavior. While use RIPk...
Source: Experimental Neurology - Category: Neurology Authors: Tags: Exp Neurol Source Type: research