Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, 900 Gajwa-dong, Jinju, South Korea.
Neurosci Lett. 2011 Jul 8;498(2):105-9. doi: 10.1016/j.neulet.2011.05.003. Epub 2011 May 8.
Nicotinamide protects cortical neuronal cells against cerebral ischemic injury through activation of various cytoprotective mechanisms. Here, this study confirmed the neuroprotective effects of nicotinamide in focal cerebral ischemic injury and investigated whether nicotinamide modulates a crucial survival pathway, Akt and its downstream targets. Adult male rats were treated with vehicle or nicotinamide (500 mg/kg) 2h after the onset of middle cerebral artery occlusion (MCAO). Brains were collected 24h after MCAO and infarct volumes were analyzed. Nicotinamide significantly reduced the infarct volume in the cerebral cortex. Potential activation was measured by phosphorylation of PDK1 at Ser(241), Akt at Ser(473), and Bad at Ser(136) using Western blot analysis. Nicotinamide prevented the injury-induced decrease of pPDK1, pAkt, and pBad levels. 14-3-3 levels were not different between vehicle- and nicotinamide-treated animals. However, pBad and 14-3-3 interaction levels decreased during MCAO, but were maintained in the presence of nicotinamide, compared to levels in control animals. These findings suggest that nicotinamide attenuates cell death due to focal cerebral ischemic injury and that neuroprotective effects are mediated through the Akt signaling pathway, thus enhancing neuronal survival.
烟酰胺通过激活多种细胞保护机制来保护皮质神经元细胞免受脑缺血性损伤。本研究证实了烟酰胺在局灶性脑缺血损伤中的神经保护作用，并研究了烟酰胺是否调节关键的存活途径 Akt 及其下游靶标。成年雄性大鼠在大脑中动脉闭塞（MCAO）后 2 小时给予载体或烟酰胺（500mg/kg）治疗。MCAO 后 24 小时收集大脑，分析梗死体积。烟酰胺显著减少大脑皮质的梗死体积。通过 PDK1 在 Ser（241）、Akt 在 Ser（473）和 Bad 在 Ser（136）的磷酸化来测量潜在的激活，使用 Western blot 分析。烟酰胺防止了损伤诱导的 pPDK1、pAkt 和 pBad 水平的降低。载体处理和烟酰胺处理的动物之间 14-3-3 水平没有差异。然而，在 MCAO 期间，pBad 和 14-3-3 相互作用水平下降，但与对照动物相比，在烟酰胺存在下得到维持。这些发现表明，烟酰胺减轻了由于局灶性脑缺血损伤引起的细胞死亡，神经保护作用是通过 Akt 信号通路介导的，从而增强神经元存活。
