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Published on: January 3, 2025
Phosphorylation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase after transient forebrain
1Department of Neurosurgery, Graduate School of Medicine, Kyoto University, 606-8507, Kyoto, Japan. takagi@helix.mgh.harvard.edu
Abstract:
We investigated the activation of c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) during transient forebrain ischemia to clarify the roles of these stress kinases during brain ischemia. Mice were subjected bilateral common carotid artery (BCCA) occlusion for 20 min followed by reperfusion. Immunohistochemical analysis and Western blot analysis for active JNK and active p38 MAPK were performed at 0, 5, 10, 30 and 150 min after reperfusion. After 5 min of reperfusion, active JNK and p38 MAPK immunoreactivities were enhanced in neurons in the cerebral cortex and hippocampus; this activation peaked at 30 min of reperfusion. Stress kinases activation dominantly occurred in the similar regions, in which neurons with fragmented DNA were detected at 72 h after reperfusion. Western blot analysis indicated that JNK 1, JNK 2 and p38 MAPK were activated at 10 and 30 min after reperfusion. These findings indicate that JNK and p38 MAPK pathways may play important roles in neuronal death during brain ischemia.
Insights
Stress kinases c-Jun NH(2)-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) are activated during brain ischemia. Their activation correlates with neuronal death, suggesting a role in ischemic brain injury.
Area of Science:
- Neuroscience
- Molecular Biology
- Pathophysiology
Background:
- Transient forebrain ischemia is a significant cause of neuronal damage.
- Stress-activated protein kinases, including JNK and p38 MAPK, are implicated in cellular stress responses.
Purpose of the Study:
- To investigate the activation patterns of JNK and p38 MAPK during transient forebrain ischemia.
- To elucidate the role of these stress kinases in neuronal death following ischemic events.
Main Methods:
- Mice underwent transient forebrain ischemia induced by bilateral common carotid artery occlusion.
- Immunohistochemistry and Western blot analyses were used to detect active JNK and p38 MAPK at various reperfusion time points.
Main Results:
- Activation of JNK and p38 MAPK was observed in neurons of the cerebral cortex and hippocampus starting at 5 minutes of reperfusion.
- Peak activation of these kinases occurred at 30 minutes of reperfusion.
- The regions with heightened stress kinase activity showed neuronal DNA fragmentation at 72 hours post-reperfusion.
Conclusions:
- JNK and p38 MAPK pathways are significantly activated during transient forebrain ischemia.
- These stress kinase pathways are likely involved in the mechanisms of neuronal death after ischemic brain injury.
