Ferulic acid prevents the cerebral ischemic injury-induced decreases of astrocytic phosphoprotein PEA-15 and its two phosphorylated forms.
Ferulic acid protects neuronal cells against focal cerebral ischemic injury through its anti-oxidative and anti-inflammatory effects. Phosphoprotein enriched in astrocytes 15 (PEA-15) is known to modulate various cellular processes including cell proliferation, apoptosis, and survival. This study was investigated whether ferulic acid can regulate the levels of PEA-15 and its two phosphorylated forms (Ser 104 and Ser 116) in a cerebral ischemic injury model and in neuronal cells exposed to glutamate. A middle cerebral artery occlusion (MCAO) was performed to induce focal cerebral ischemic injury. Adult male rats were immediately treated with vehicle or ferulic acid (100 mg/kg) at the beginning of the MCAO, and then cerebral cortices were collected 24h after MCAO. The decrease in PEA-15 level after ischemic injury was detected using a proteomic approach. Ferulic acid administration prevented the ischemic injury-induced decrease of PEA-15 level. Moreover, Western blot analysis clearly confirmed that ferulic acid attenuates the ischemic injury-induced decreases in PEA-15, phospho-PEA-15 (Ser 104), and phospho-PEA-15 (Ser 116) levels. Glutamate exposure induced significant reductions in the levels of PEA-15 and the two phospho-PEA-15 (Ser 104 and Ser 116) in cultured hippocampal neuron, while pretreatment with ferulic acid prevented the glutamate toxicity-induced decreases in these proteins levels. The decrease of phospho-PEA-15 protein level indicates that the anti-apoptotic function of PEA-15 was being inhibited. Thus, these results suggest that ferulic acid protects neuronal cells against ischemic injury by maintenance of phospho-PEA-15 protein levels.
Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea. pokoh@gnu.ac.kr
Phil-Ok
PO
Koh
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D002460:Cell Line; D002540:Cerebral Cortex / Q000378:metabolism; D003373:Coumaric Acids / Q000494:pharmacology*; D018698:Glutamic Acid / Q000633:toxicity; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley
D051017:Apoptosis Regulatory Proteins; D003373:Coumaric Acids; D018696:Neuroprotective Agents; C490443:Pea15 protein, rat; D010750:Phosphoproteins; D018698:Glutamic Acid; C004999:ferulic acid