Phosphorylation of c-Jun NH(2)-terminal kinase and p38 mitogen-activated protein kinase after transient forebrain ischemia in mice.
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.
Takagi
Y
Y
Department of Neurosurgery, Graduate School of Medicine, Kyoto University, 606-8507, Kyoto, Japan. takagi@helix.mgh.harvard.edu
Nozaki
K
K
Sugino
T
T
Hattori
I
I
Hashimoto
N
N
D000818:Animals; D017209:Apoptosis; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000201:enzymology / Q000473:pathology; D053938:DNA Fragmentation; D006624:Hippocampus / Q000201:enzymology / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000201:enzymology*; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009474:Neurons / Q000201:enzymology / Q000473:pathology; D010766:Phosphorylation; D016548:Prosencephalon / Q000098:blood supply / Q000201:enzymology* / Q000473:pathology; D015398:Signal Transduction; D048051:p38 Mitogen-Activated Protein Kinases
D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases