Koh Phil-Ok
Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju 660–701, South Korea.
J Vet Med Sci. 2012 Mar;74(3):377-80. doi: 10.1292/jvms.11-0392. Epub 2011 Nov 8.
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.
烟酰胺对局灶性脑缺血损伤具有神经保护作用。富含星形胶质细胞的磷蛋白15（PEA - 15）在具有广泛抗凋亡功能的星形胶质细胞中显著表达。本研究调查了在大脑中动脉闭塞（MCAO）诱导损伤的动物模型中，烟酰胺是否调节PEA - 15以及两种磷酸化PEA - 15（丝氨酸104和116）的水平。成年雄性大鼠在MCAO发作后2小时接受载体或烟酰胺（500 mg/kg）治疗，并在MCAO后24小时收集大脑皮层。采用蛋白质组学方法，MCAO导致PEA - 15水平降低，而烟酰胺治疗减轻了损伤诱导的PEA - 15降低。蛋白质印迹分析结果表明，烟酰胺可防止损伤诱导的磷酸化PEA - 15（丝氨酸104）和磷酸化PEA - 15（丝氨酸116）水平降低。PEA - 15的磷酸化发挥抗凋亡功能，而PEA - 15磷酸化的降低会导致凋亡细胞死亡。这些结果表明，烟酰胺通过减轻损伤诱导的PEA - 15和磷酸化PEA - 15（丝氨酸104和丝氨酸116）蛋白降低而发挥神经保护作用。
