Modulation of ERK and JNK activity by transient forebrain ischemia in rats.

The mitogen-activated protein (MAP) kinase families of ERK and JNK participate in numerous intracellular signaling pathways and are abundantly expressed in the CNS. Activation of ERK and JNK during reperfusion of ischemic tissue is implicated in promoting cell death, insofar as inhibition of either pathway reduces neuronal cell death. However, ERK or JNK activation provides protection in other neuronal injury models. In this study, we monitored the concurrent modulation of ERK and JNK activity in the hippocampus, neocortex, and striatum during ischemia and immediately upon reperfusion in a rat model of transient global ischemia. All three regions incur a similar reduction in blood flow during occlusion but show different extents and temporal patterns of injury following reperfusion. ERK and JNK were active in the normal rat forebrain, and phosphorylation was reduced by ischemia. Upon reperfusion, ERK was rapidly activated in the hippocampus, neocortex, and striatum, whereas JNK phosphorylation increased in the hippocampus and striatum but not in the neocortex. The response of JNK vs. ERK more closely reflects the susceptibility of these regions. JNK1 was the predominant phosphorylated isoform. A minor pool of phosphorylated JNK3 increased above the control level after reperfusion in hippocampal but not in neocortical particulate fractions. In addition, a novel 32-35-kDa c-Jun kinase activity was detected in the hippocampus, neocortex, and striatum. The results show that ERK and JNK activities are rapidly, but not identically, modulated by ischemia and reperfusion and indicate that the MAP kinase pathways contribute to regulating the response to acute CNS injury.

Shackelford DA ，Yeh RY 《JOURNAL OF NEUROSCIENCE RESEARCH》

Alteration of MAP kinase pathways after transient forebrain ischemia.

Hu BR ，Liu CL ，Park DJ 《JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM》

Effects of hepatocyte growth factor on phosphorylation of extracellular signal-regulated kinase and hippocampal cell death in rats with transient forebrain ischemia.

Niimura M ，Takagi N ，Takagi K ，Funakoshi H ，Nakamura T ，Takeo S ... -  《EUROPEAN JOURNAL OF PHARMACOLOGY》

Activation of ERK and JNK MAP kinases in optic nerves of rats exposed to global cerebral ischemia.

Mrsić-Pelcić J ，Pelcić G ，Vitezić D ，Ljubicić D ，Zupan G ，Simonić A ... -  《Psychiatria Danubina》

Differential early mitogen-activated protein kinase activation in hyperglycemic ischemic brain injury in the rat.

Farrokhnia N ，Roos MW ，Terént A ，Lennmyr F ... -  《EUROPEAN JOURNAL OF CLINICAL INVESTIGATION》