title: Nicotinamide attenuates the decrease of astrocytic phosphoprotein PEA-15 in focal cerebral ischemic injury.
abstract: Nicotinamide exerts neuroprotective effects against focal cerebral ischemic injury. Phosphoprotein enriched in astrocytes 15 (PEA-15) is prominently expressed in astrocytes that exert broad anti-apoptotic functions. This study investigated whether nicotinamide modulates PEA-15 and levels of two phosphorylated PEA-15 (Serine 104 and 116) in an animal model of middle cerebral artery occlusion (MCAO)-induced injury. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2 hr after the onset of MCAO and cerebral cortices were collected at 24 hr after MCAO. In a proteomic approach, MCAO induced decreases of PEA-15 levels, while nicotinamide treatment attenuated the injury-induced decrease in PEA-15. The results of Western blot analysis suggest that nicotinamide prevented injury-induced reduction in phospho-PEA-15 (Serine 104) and phospho-PEA-15 (Serine 116) levels. The phosphorylation of PEA-15 exerts anti-apoptotic functions, and reduction of PEA-15 phosphorylation leads to apoptotic cell death. These results suggest that nicotinamide exerts a neuroprotective effect by attenuating the injury-induced decreases of PEA-15 and phospho-PEA-15 (Ser 104 and Ser 116) proteins.
authors: Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660–701, South Korea. pokoh@gnu.ac.kr
authors: Phil-Ok
authors: PO
authors: Koh
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002545:Brain Ischemia / Q000188:drug therapy*; D005786:Gene Expression Regulation / Q000187:drug effects; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D009536:Niacinamide / Q000494:pharmacology*; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014803:Vitamin B Complex / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D018696:Neuroprotective Agents; C490443:Pea15 protein, rat; D010750:Phosphoproteins; D014803:Vitamin B Complex; D009536:Niacinamide