Direkt zum Inhalt
Merck

Downregulation of PEBP1 in rat brain cortex in hypoxia.

Journal of molecular neuroscience : MN (2009-08-26)
Sandeepta Burgula, Rajesh Medisetty, Nalini Jammulamadaka, Sairam Musturi, Govindan Ilavazhagan, Surya S Singh
ZUSAMMENFASSUNG

In order to understand dementia and other ailments associated with high altitude hypoxia, adult Sprague Dawley male rats were exposed to simulated conditions of high altitude (7,500 m above sea level, 59 mmHg) for a period of 5 days and analyzed for changes in neuronal proteome by 2-D sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein extracts obtained from the brain cortex and hippocampus of the hypoxic rats were separated by 2-D gel electrophoresis. Differentially expressed proteins (analysis by 2-D gel analysis software, Bio-2D, Vilber-Lourmat, France and Delta2d, Decodon, Germany) were subjected to matrix-assisted laser desorption/ionization time-of-flight analysis. Among the proteins identified, the spot corresponding to pI 5.4 and molecular weight 21 kDa, identified as phosphatidylethanolamine binding protein (PEBP1), was consistently lowered (54%) in hypoxic cortex samples. PEBP1, also known as Raf kinase inhibitor protein, is a precursor of hippocampus cholinergic neurostimulatory peptide (HCNP). Western blot analysis revealed elevated phospho-extracellular signal-regulated kinase in hypoxic rat cortex samples, indicating activation of Raf/mitogen-activated protein kinase pathway under hypoxia. Lowered HCNP levels leading to 23% decrease in choline acetyltransferase and 63% increase in acetylcholinesterase activity were detected in hypoxic rat brain cortex, while no significant change was noted in hippocampus. Since PEBP1 is lowered in a number of neurological disorders associated with dementia, we speculate that lowered expression of PEBP1 might be responsible for dementia associated with high-altitude hypoxia. Further studies targeting PEBP1 might give clues about signaling pathways associated with hypoxia and dementia.