The potential role of HO-1 in regulating the MLK3-MKK7-JNK3 module scaffolded by JIP1 during cerebral ischemia/reperfusion in rats
The potential role of HO-1 in regulating the MLK3-MKK7-JNK3 module scaffolded by JIP1 during cerebral ischemia/reperfusion in rats
复制标题
HO-1 在大鼠脑缺血/再灌注期间调节 JIP1 支架的 MLK3-MKK7-JNK3 模块中的潜在作用。
DOI：
10.1016/j.bbr.2018.11.003
复制
发表时间：
2019-02-01
影响因子：
2.7
通讯作者：
Wang, Yu-Lan
中科院分区：
文献类型：
--
作者：
Song, Yuan-Jian;Dai, Chun-Xiao;Wang, Yu-Lan
血红素加氧酶（HO-1）是一种可有效减少缺血性卒中的神经保护剂，可由氯化钴原卟啉IX （CoPPIX）或罗格列酮（Ros）诱导。既往研究表明，HO-1的神经保护机制与JNK信号传导有关。HO-1的表达通过JNK信号通路保护细胞免于死亡。本研究旨在确定HO-1的神经保护作用是否依赖于JIP1所支撑的MLK3-MKK7-JNK3信号模块的组装，进而影响通过HO-1介导的JNK信号传递。缺血再灌注实验前，连续5天经侧脑室注射CoPPIX，或在短暂缺血前一周通过腹腔注射Ros。我们的研究结果表明，HO-1可以抑制由JIP1支撑的MLK3-MKK7-JNK3信号模块的组装，并最终降低JNK3的磷酸化。此外，JNK3磷酸化的抑制下调了海马CA1中p-c-Jun的水平，并增加了神经元细胞的死亡。综上所述，这些研究结果表明，HO-1可以通过调节脑缺血/再灌注时由JIP1和JNK信号支撑的MLK3-MKK7-JNK3信号模块来改善脑损伤。
Heme oxygenase (HO-1), which may be induced by Cobaltic protoporphyrin IX chloride (CoPPIX) or Rosiglitazone (Ros), is a neuroprotective agent that effectively reduces ischemic stroke. Previous studies have shown that the neuroprotective mechanisms of HO-1 are related to JNK signaling. The expression of HO-1 protects cells from death through the JNK signaling pathway. This study aimed to ascertain whether the neuroprotective effect of HO-1 depends on the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and further influences the JNK signal transmission through HO-1. Prior to the ischemia-reperfusion experiment, CoPPIX was injected through the lateral ventricle for 5 consecutive days or Ros was administered via intraperitoneal administration in the week prior to transient ischemia. Our results demonstrated that HO-1 could inhibit the assembly of the MLK3-MKK7-JNK3 signaling module scaffolded by JIP1 and could ultimately diminish the phosphorylation of JNK3. Furthermore, the inhibition of JNK3 phosphorylation downregulated the level of p-c-Jun and elevated neuronal cell death in the CA1 of the hippocampus. Taken together, these findings suggested that HO-1 could ameliorate brain injury by regulating the MLK3-MKK7-JNK3 signaling module, which was scaffolded by JIP1 and JNK signaling during cerebral ischemia/reperfusion.