Phosphorylation of extracellular signal-regulated kinase after transient cerebral ischemia in hyperglycemic rats.
The present study was undertaken to investigate whether extracellular signal-regulated kinase (ERK) was involved in mediating hyperglycemia-exaggerated cerebral ischemic damage. Phosphorylation of ERK 1/2 was studied by immunocytochemistry and by Western blot analyses. Rats were subjected to 15 min of forebrain ischemia, followed by 0.5, 1, and 3 h of reperfusion under normoglycemic and hyperglycemic conditions. The results showed that in normoglycemic animals, moderate phosphorylation of ERK 1/2 was transiently induced after 0.5 h of recovery in cingulate cortex and in dentate gyrus, returning to control values thereafter. In hyperglycemic animals, phosphorylation of ERK 1/2 was markedly increased in the cingulate cortex and dentate gyrus after 0.5 h of recovery, the increases being sustained for at least 3 h after reperfusion. Hyperglycemia also induced phosphorylation of ERK 1/2 in the hippocampal CA3 sector but not in the CA1 area. Thus, the distribution of phospho-ERK 1/2 coincides with hyperglycemia-recruited damage structures. The results suggest that hyperglycemia may influence the outcome of an ischemic insult by modulating signal transduction pathways involving ERK 1/2.
Li
P A
PA
Center for the Study of Neurological Disease, The Queen's Medical Center, Honolulu, Hawaii, USA.
He
Q P
QP
Yi-Bing
O
O
Hu
B R
BR
Siesjö
B K
BK
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001921:Brain / Q000473:pathology; D002467:Cell Nucleus / Q000378:metabolism; D006943:Hyperglycemia / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D008297:Male; D018613:Microscopy, Confocal; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D001786:Blood Glucose; D020928:Mitogen-Activated Protein Kinases