Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
Neurosci Lett. 2013 Jun 17;545:6-10. doi: 10.1016/j.neulet.2013.04.010. Epub 2013 Apr 19.
Nicotinamide is an important cofactor in the prevention of brain damage during focal cerebral ischemia. Hippocalcin is a calcium buffer protein that modulates intracellular calcium concentration and attenuates apoptosis. In this study, we investigated whether nicotinamide modulates hippocalcin expression during cerebral ischemia. Male Sprague-Dawley rats were treated with vehicle or nicotinamide (500 mg/kg) 2 h after the onset of middle cerebral artery occlusion (MCAO) and cerebral cortex tissues were collected 24 h after MCAO. Nicotinamide treatment decreased infarct volume in the cerebral cortex of MCAO-operated animals. Our proteomic approach revealed a decrease in hippocalcin expression in vehicle-treated animals during MCAO, which was attenuated by nicotinamide treatment. We used RT-PCR and Western blot analyses to demonstrate that nicotinamide clearly restored the injury-induced decrease in hippocalcin expression. Glutamate toxicity also decreased hippocalcin levels in cultured hippocampal cells, while nicotinamide treatment prevented the glutamate exposure-induced decrease in hippocalcin levels. These results suggest that nicotinamide modulates hippocalcin expression in cerebral ischemic injury and consequently contributes to the prevention of neuronal cell death.
烟酰胺是预防局灶性脑缺血时脑损伤的重要辅酶。钙调蛋白是一种钙缓冲蛋白，可调节细胞内钙浓度并减轻细胞凋亡。在这项研究中，我们研究了烟酰胺是否在脑缺血期间调节钙调蛋白的表达。雄性 Sprague-Dawley 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）处理，并在 MCAO 后 24 小时收集大脑皮质组织。烟酰胺治疗可减少 MCAO 动物大脑皮质的梗死体积。我们的蛋白质组学方法显示，在 MCAO 期间，载体处理的动物中钙调蛋白表达减少，而烟酰胺治疗可减轻这种减少。我们使用 RT-PCR 和 Western blot 分析表明，烟酰胺可明显恢复损伤诱导的钙调蛋白表达减少。谷氨酸毒性也降低了培养的海马细胞中的钙调蛋白水平，而烟酰胺处理可防止谷氨酸暴露诱导的钙调蛋白水平降低。这些结果表明，烟酰胺可调节脑缺血损伤中的钙调蛋白表达，从而有助于预防神经元细胞死亡。
