Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
J Pineal Res. 2011 Nov;51(4):381-6. doi: 10.1111/j.1600-079X.2011.00900.x. Epub 2011 May 27.
Melatonin functions as a free-radical scavenger and has a neuroprotective effect against ischemic brain damage. PEA-15 (phosphoprotein enriched in astrocytes 15) regulates various cellular processes including cell proliferation and apoptosis. In this study, we investigated whether melatonin regulates the levels of PEA-15 and the two phosphorylated forms of PEA-15 (Ser 104 and Ser 116) in a middle cerebral artery occlusion (MCAO)-induced injury model and neuronal cells exposed to glutamate. Adult male rats were treated with vehicle or melatonin (5 mg/kg) prior to MCAO, and cerebral cortex tissues were collected 24 h after MCAO. PEA-15 levels after ischemic brain injury were monitored using a proteomic approach. Melatonin pretreatment prevented the ischemic injury-induced reduction in PEA-15 levels. Moreover, Western blot analysis demonstrated that melatonin attenuated the ischemic injury-induced reduction in PEA-15, phospho-PEA-15 (Ser 104), and phospho-PEA-15 (Ser 116) levels. Neuronal cells exposed to glutamate showed decreased expression of PEA-15, phospho-PEA-15 (Ser 104), and phospho-PEA-15 (Ser 116), while melatonin pretreatment prevented the glutamate toxicity-induced decreases in the levels of these proteins. The reduction in the levels of phospho-PEA-15 proteins indicates the inhibition of anti-apoptotic function of PEA-15. Together, in vivo and in vitro results suggest that melatonin protects neurons against ischemic injury by maintaining levels of phospho-PEA-15 proteins.
褪黑素作为一种自由基清除剂，具有对抗缺血性脑损伤的神经保护作用。PEA-15（富含星形胶质细胞的磷蛋白 15）调节包括细胞增殖和细胞凋亡在内的各种细胞过程。在这项研究中，我们研究了褪黑素是否调节了在大脑中动脉闭塞（MCAO）诱导的损伤模型和谷氨酸暴露的神经元细胞中 PEA-15 及其两种磷酸化形式（Ser104 和 Ser116）的水平。成年雄性大鼠在 MCAO 前用载体或褪黑素（5mg/kg）处理，并在 MCAO 后 24 小时收集大脑皮质组织。使用蛋白质组学方法监测缺血性脑损伤后 PEA-15 的水平。褪黑素预处理可防止缺血性损伤引起的 PEA-15 水平降低。此外，Western blot 分析表明，褪黑素减弱了缺血性损伤引起的 PEA-15、磷酸化 PEA-15（Ser104）和磷酸化 PEA-15（Ser116）水平的降低。谷氨酸暴露的神经元细胞显示 PEA-15、磷酸化 PEA-15（Ser104）和磷酸化 PEA-15（Ser116）的表达降低，而褪黑素预处理可防止这些蛋白水平因谷氨酸毒性而降低。磷酸化 PEA-15 蛋白水平的降低表明 PEA-15 的抗细胞凋亡功能受到抑制。总之，体内和体外结果表明，褪黑素通过维持磷酸化 PEA-15 蛋白水平来保护神经元免受缺血性损伤。
