Transient forebrain ischemia induced phosphorylation of cAMP-responsive element-binding protein is suppressed by hyperglycemia.
Hyperglycemia enhances brain damage due to transient cerebral ischemic stroke. The hyperglycemia-mediated detrimental effect is probably due to mitochondrial dysfunction and the resulting promotion of cell death pathways. In this study, we determined whether hyperglycemia suppresses cell survival signals that involve the cAMP-responsive element-binding protein (CREB) and activating transcription factor (ATF-2). Total and phosphorylated CREB and ATF-2 were measured in the cingulate cortex and dentate gyrus, two structures that are ischemia-resistant under normoglycemic conditions but become ischemia-vulnerable under hyperglycemic conditions, using immunocytochemistry and Western blot analysis. Samples were collected from normo-operated and hyperglycemic rats subjected to 15 min of ischemia followed by reperfusion. Transient ischemia induced a persistent phosphorylation of CREB in normoglycemic animals. Hyperglycemia suppressed phosphorylation of CREB in hyperglycemia-recruited areas. Ischemia also induced a transient increase of phospho-ATF-2 in the cingulated cortex that was suppressed by hyperglycmia. We conclude that suppression of neuronal survival signals by hyperglycemia may contribute to the mechanism of converting ischemia-resistant structures into vulnerable ones.
He
Qingping
Q
Pacific Biomedical Research Center and John A Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USA.
Csiszar
Katalin
K
Li
Ping- An
P
D051698:Activating Transcription Factor 2; D000818:Animals; D002470:Cell Survival / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006179:Gyrus Cinguli / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D006943:Hyperglycemia / Q000378:metabolism* / Q000503:physiopathology; D007150:Immunohistochemistry; D002546:Ischemic Attack, Transient / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D009410:Nerve Degeneration / Q000378:metabolism* / Q000503:physiopathology; D010766:Phosphorylation; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000378:metabolism / Q000503:physiopathology; D014157:Transcription Factors / Q000378:metabolism*
D051698:Activating Transcription Factor 2; C497107:Atf2 protein, rat; D017362:Cyclic AMP Response Element-Binding Protein; D014157:Transcription Factors