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CREB-mediated Bcl-2 protein expression after ischemic preconditioning.

Robert Meller·Manabu Minami·Jennifer A Cameron·Soren Impey·Dexi Chen·Jing-Quan Lan·David C Henshall·Roger P Simon
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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.

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AnimalsBlotting, WesternBrain IschemiaCells, CulturedCyclic AMP Response Element-Binding ProteinElectrophoretic Mobility Shift AssayImmunohistochemistryIn Situ Nick-End LabelingIntracellular Signaling Peptides and ProteinsIschemic PreconditioningMaleNeuronsProtein KinasesProto-Oncogene Proteins c-bcl-2RatsJournal ArticleResearch Support, U.S. Gov't, P.H.S.

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Robert Meller, Manabu Minami, Jennifer A Cameron, Soren Impey, Dexi Chen, Jing-Quan Lan, David C Henshall, Roger P Simon. 2005. CREB-mediated Bcl-2 protein expression after ischemic preconditioning.. https://doi.org/10.1038/sj.jcbfm.9600024

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