Cerebral postischemic reperfusion-induced demethylation of the protein phosphatase 2A catalytic subunit.

Abstract

Brain reperfusion after a period of global ischemia induces changes in the phosphorylation state of a great number of proteins. Neuronal responses to ischemia and reperfusion are quite different depending on the brain region, and phosphorylation changes may be implicated in this tissue-specific response. For this reason, we have used both biochemical and immunohistochemical methods to investigate the potential role of PP2A, the most abundant Ser/Thr phosphatase in the brain, in ischemic injury. PP2A activity as measured with phosphorylase a as substrate was slightly inhibited after 30 min ischemia followed by 30 min reperfusion, and this inhibition correlated with an increased S6K1 and ERK1/2 phosphorylation. Using a monoclonal antibody unable to recognize the methylated form of PP2Ac, we demonstrated that the catalytic subunit of PP2A (PP2Ac) was highly methylated in the brain. In addition, the postischemic reperfusion-induced changes in PP2Ac methylation were studied in sections from cerebral cortex, hippocampus and striatum. Regional differences in PP2Ac methylation were observed within control brains, and the postischemic reperfusion caused a generalized demethylation of PP2Ac. Those regions in the control brains containing highest levels of methylated PP2Ac were the most intensively demethylated after reperfusion and corresponded to the regions most vulnerable to ischemic damage.

• Authors: Cristina Martín de la Vega, Jozef Burda, M V Toledo Lobo, Matilde Salinas
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 69 Issue 4 Pg. 540-9 (Aug 15 2002) ISSN: 0360-4012 [Print] United States
• PMID: 12210847 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright 2002 Wiley-Liss, Inc.

Chemical References

• Protein Isoforms
• Ribosomal Protein S6 Kinases
• Mitogen-Activated Protein Kinases
• Phosphoprotein Phosphatases
• Protein Phosphatase 2

Topics

• Animals
• Brain Ischemia (enzymology, physiopathology)
• Catalytic Domain (physiology)
• Cerebral Cortex (enzymology, physiopathology)
• Corpus Striatum (enzymology, physiopathology)
• Disease Models, Animal
• Hippocampus (enzymology, physiopathology)
• Immunohistochemistry
• Methylation
• Mitogen-Activated Protein Kinases (metabolism)
• Neurons (enzymology)
• Phosphoprotein Phosphatases (metabolism)
• Protein Isoforms (metabolism)
• Protein Phosphatase 2
• Rats
• Rats, Wistar
• Reperfusion Injury (enzymology, physiopathology)
• Ribosomal Protein S6 Kinases (metabolism)
• Telencephalon (enzymology, physiopathology)