Department of Anatomy, College of Veterinary Medicine, Research Institute of Life Science, Gyeongsang National University, Jinju, 660-701, South Korea.
Synapse. 2013 Jul;67(7):390-8. doi: 10.1002/syn.21649. Epub 2013 Mar 7.
Intracellular calcium overload is a critical pathophysiological factor in ischemic injury. Hippocalcin is a neuronal calcium sensor protein that buffers intracellular calcium levels and protects cells from apoptotic stimuli. Ferulic acid exerts a neuroprotective effect in cerebral ischemia through its anti-oxidant and anti-inflammation activity. This study investigated whether ferulic acid contributes to hippocalcin expression during cerebral ischemia and glutamate exposure-induced neuronal cell death. Rats were immediately treated with vehicle or ferulic acid (100 mg/kg, i.v.) after middle cerebral artery occlusion (MCAO). Brain tissues were collected 24 h after MCAO and followed by assessment of cerebral infarct. Ferulic acid reduced MCAO-induced infarct regions. A proteomics approach elucidated a decrease in hippocalcin in MCAO-operated animals, ferulic acid attenuates the injury-induced decrease in hippocalcin expression. Reverse transcription-polymerase chain reaction and Western blot analyses confirmed that ferulic acid prevents the injury-induced decrease in hippocalcin. In cultured HT22 hippocampal cells, glutamate exposure increased the intracellular Ca(2+) levels, whereas ferulic acid attenuated this increase. Moreover, ferulic acid attenuated the glutamate toxicity-induced decrease in hippocalcin expression. These findings can suggest the possibility that ferulic acid exerts a neuroprotective effect through modulating hippocalcine expression and regulating intracellular calcium levels.
细胞内钙超载是缺血性损伤的一个关键病理生理因素。钙调蛋白是一种神经元钙传感器蛋白，可缓冲细胞内钙水平并防止细胞受到凋亡刺激。阿魏酸通过其抗氧化和抗炎活性在脑缺血中发挥神经保护作用。本研究探讨了阿魏酸是否有助于脑缺血和谷氨酸暴露诱导的神经元细胞死亡过程中钙调蛋白的表达。大脑中动脉闭塞（MCAO）后，大鼠立即给予载体或阿魏酸（100mg/kg，iv）治疗。MCAO 后 24 小时采集脑组织，并评估脑梗死。阿魏酸减少 MCAO 引起的梗死区域。蛋白质组学方法阐明了 MCAO 动物中海马钙调蛋白表达减少，阿魏酸减轻了损伤引起的海马钙调蛋白表达减少。逆转录-聚合酶链反应和 Western blot 分析证实，阿魏酸可防止损伤引起的海马钙调蛋白减少。在培养的 HT22 海马细胞中，谷氨酸暴露增加细胞内 Ca(2+)水平，而阿魏酸可减弱这种增加。此外，阿魏酸减弱了谷氨酸毒性诱导的海马钙调蛋白表达减少。这些发现提示阿魏酸可能通过调节钙调蛋白表达和调节细胞内钙水平发挥神经保护作用。
