Effects of hyperglycemic and normoglycemic cerebral ischemia on phosphorylation of c-jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK).
Transient global cerebral ischemia leads to delayed neuronal cell death in the hippocampal CA1, caudate putamen and neocortex. If preischemic hyperglycemia exists, the same duration of ischemia recruits additional brain structures, such as dentate gyrus to become damaged. The objective of the present study is to determine whether activation of mitogen-activated protein kinases (MAPKs) plays a role in hyperglycemia-mediated ischemic neuronal damage. Using phopho-specific antibodies against c-jun NH2-terminal kinase (JNK) and p38 MAPK, we studied activation of these two MAPKs in ischemia-vulnerable neocortex and ischemia-resistant dentate gyrus in rats subjected to 15 min of forebrain ischemia and followed by 0.5, 1 and 3 hr of recirculation under normo- and hyperglycemic conditions. The results showed that levels of phosphorylated JNK increased in both normo- and hyperglycemic brains following blood reperfusion for 0.5 hr and persisted up to 3 hr in the neocortex but not in the dentate gyrus, implying JNK may play a role in mediating neuronal cell death after ischemia. However, since hyperglycemia did not further increase phospho-JNK, JNK may not contribute to the detrimental effect of hyperglycemia on neuronal cell death. The amount of phospho-p38 was not altered by ischemia under both normo- and hyperglycemic conditions, suggesting that p38 MAPK may not play a major role in mediating neuronal damage in these two structures.
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Cardiovascular Research Center, Pacific Biomedical Research Center & John A. Burns School of Medicine, University of Hawaii at Manoa, Biomed Tower Room T410, 1960 East-West Road, Honolulu, HI 96822, USA.
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D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D016923:Cell Death; D018891:Dentate Gyrus / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D004789:Enzyme Activation; D006943:Hyperglycemia / Q000473:pathology*; D048031:JNK Mitogen-Activated Protein Kinases; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D019579:Neocortex / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D009474:Neurons / Q000201:enzymology / Q000378:metabolism / Q000473:pathology*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D048051:p38 Mitogen-Activated Protein Kinases
D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases