The ERK5-MEF2C transcription factor pathway contributes to anti-apoptotic effect of cerebral ischemia preconditioning in the hippocampal CA1 region of rats.

Abstract

The purpose of the present study was to investigate the role of myocyte enhancer binding factor 2C (MEF2C), a common substrate of p38 kinase and extracellular signal-regulated kinase 5 (ERK5) in the hippocampal CA1 region following cerebral ischemia preconditioning (CIP) and without CIP. In animals that did not undergo preconditioning, MEF2C was significantly activated with an early peak at 30 min of reperfusion, which was followed by a pronounced decrease of MEF2C protein levels in the late phase of reperfusion (3-5 d). Co-immunoprecipitation studies failed to show an interaction between ERK5 and MEF2C, and ERK5-antisense oligonucleotide (ERK5-AS) had no effect on MEF2C activation, suggesting that the MEF2C activation is mediated by a kinase other than ERK5. Following preconditioning (3 min ischemia), MEF2C was strongly activated during the late stage of reperfusion (6 h-5 d). Co-immunoprecipitation studies showed that the interaction of ERK5 and MEF2C significantly increased at 3 d of reperfusion, and this increase was markedly inhibited by ERK5-AS. Inhibition of the ERK5-MEF2C pathway resulted in a significant increase in the number of TUNEL-positive apoptotic cells compared with CIP groups in the hippocampal CA1 region, and abolished the neuroprotective effect induced by CIP. Taken together, these results demonstrate that ERK5-MEF2C signaling is significantly enhanced in the hippocampus CA1 following CIP, and that ERK5-MEF2C signaling plays a critical role in the mediation of the anti-apoptotic and neuroprotective actions of ischemic preconditioning.

• Authors: Rui-Min Wang, Quan-Guang Zhang, Jie Li, Li-Cai Yang, Fang Yang, Darrell W Brann
• Journal: Brain research (Brain Res) Vol. 1255 Pg. 32-41 (Feb 19 2009) ISSN: 1872-6240 [Electronic] Netherlands
• PMID: 19103177 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• MEF2 Transcription Factors
• Myogenic Regulatory Factors
• Mitogen-Activated Protein Kinase 7

Topics

• Animals
• Apoptosis
• Blotting, Western
• Brain Ischemia (enzymology, pathology, prevention & control)
• Cell Death
• Cytoprotection
• Hippocampus (enzymology, pathology)
• Immunohistochemistry
• Immunoprecipitation
• In Situ Nick-End Labeling
• Ischemic Preconditioning (methods)
• MEF2 Transcription Factors
• Male
• Mitogen-Activated Protein Kinase 7 (metabolism)
• Myogenic Regulatory Factors (metabolism)
• Rats
• Rats, Sprague-Dawley
• Reperfusion (adverse effects)
• Reperfusion Injury (enzymology, pathology, prevention & control)
• Signal Transduction
• Time Factors