We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
CREB-mediated Bcl-2 protein expression after ischemic preconditioning.
- Authors
Meller, Robert; Minami, Manabu; Cameron, Jennifer A; Impey, Soren; Chen, Dexi; Lan, Jing-Quan; Henshall, David C; Simon, Roger P
- Abstract
Bcl-2 plays a pivotal role in the control of cell death and is upregulated by ischemic tolerance. Because Bcl-2 expression is regulated by the transcription factor cyclic AMP response element-binding protein (CREB), we investigated the role of CREB activation in two models of ischemic preconditioning: focal ischemic tolerance after middle cerebral artery occlusion (MCAO) and in vitro ischemic tolerance modeled by oxygen-glucose deprivation (OGD). After preconditioning ischemia (30 minutes MCAO or 30 minutes OGD), phosphorylation of CREB was increased, and there was an increased interaction between the bcl-2 cyclic AMP-responsive element (CRE) promoter and nuclear proteins after preconditioning ischemia in vivo and in vitro. Chromatin immunoprecipitation revealed an increased interaction between CREB-binding protein and the bcl-2 CRE rather than CREB, after preconditioning ischemia. Ischemic tolerance was blocked by a CRE decoy oligonucleotide, which also blocked Bcl-2 expression. The protein kinase A inhibitor H89, the calcium/calmodulin kinase inhibitor KN62, and the MEK inhibitor U0126 blocked ischemic tolerance, but not the phosphatidylinositol 3-kinase inhibitor LY294002. H89, KN62, and U0126 reduced CREB activation and Bcl-2 expression. Taken together, these data suggest that after ischemic preconditioning CREB activation regulates the expression of the prosurvival protein Bcl-2.
- Publication
Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2005, Vol 25, Issue 2, p234
- ISSN
0271-678X
- Publication type
Journal Article
- DOI
10.1038/sj.jcbfm.9600024