The role of the cyclic AMP-responsive element binding protein (CREB) in hypoxic-ischemic brain damage and repair.
The cyclic AMP-responsive element binding protein (CREB) is a basally expressed, post-translationally activated transcription factor that has been implicated in the trans-activation of a number of genes in response to cAMP and calcium signals. A unilateral hypoxic-ischemic (HI) injury in the 21 day old rat was used to examine a potential role for CREB (phosphorylated and unphosphorylated) in neuronal programmed cell death or cell survival. The selectively vulnerable CAI pyramidal cells, which undergo delayed neuronal death following mild HI, show a loss of CREB and phosphorylated CREB (pCREB) immunoreactivity on the injured side 48 and 72 h following HI. In contrast the resistant dentate granule cells and cortical cells produce a bimodal increase in pCREB immunoreactivity, peaking 6 and 48 h following HI. The fact that cells surviving the HI insult are showing increased activation of CREB suggests that this protein might be involved in the process of neuroprotection.
Walton
M
M
Department of Pharmacology and Clinical Pharmacology, Faculty of Medicine and Health Science, University of Auckland, New Zealand.
Sirimanne
E
E
Williams
C
C
Gluckman
P
P
Dragunow
M
M
D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D051381:Rats; D017208:Rats, Wistar
D002352:Carrier Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D000242:Cyclic AMP