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Related Experiment Videos

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

Robert Meller1, Manabu Minami, Jennifer A Cameron

  • 1RS Dow Neurobiology Laboratories, Legacy Research, Portland, Oregon 97232, USA. rmeller@downeurobiology.org

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
|January 14, 2005
PubMed
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Cyclic AMP response element-binding protein (CREB) activation enhances ischemic tolerance by upregulating the prosurvival protein Bcl-2. This occurs through CREB

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Death Research

Background:

  • Bcl-2 is crucial for controlling cell death and is upregulated by ischemic tolerance.
  • Bcl-2 expression is regulated by the transcription factor cyclic AMP response element-binding protein (CREB).

Purpose of the Study:

  • To investigate the role of CREB activation in ischemic preconditioning.
  • To examine CREB's role in focal ischemic tolerance (middle cerebral artery occlusion - MCAO) and in vitro ischemic tolerance (oxygen-glucose deprivation - OGD).

Main Methods:

  • Used MCAO and OGD models for ischemic preconditioning.
  • Assessed CREB phosphorylation and interaction with the bcl-2 cyclic AMP-responsive element (CRE) promoter via chromatin immunoprecipitation.
  • Utilized CRE decoy oligonucleotide and specific kinase inhibitors (H89, KN62, U0126, LY294002).

Related Experiment Videos

Main Results:

  • Preconditioning ischemia increased CREB phosphorylation and interaction with the bcl-2 CRE promoter.
  • CREB-binding protein interaction with the bcl-2 CRE was enhanced post-ischemia.
  • Blocking CRE or specific kinases (PKA, CaMK, MEK) inhibited ischemic tolerance and Bcl-2 expression.

Conclusions:

  • CREB activation is a key regulator of Bcl-2 expression following ischemic preconditioning.
  • This pathway contributes to the development of ischemic tolerance.
  • Targeting CREB activation may offer therapeutic strategies for stroke and other ischemic conditions.