Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea.
J Pineal Res. 2012 Jan;52(1):57-61. doi: 10.1111/j.1600-079X.2011.00918.x. Epub 2011 Jul 26.
Melatonin is an antioxidant that has neuroprotective functions in ischemic brain injury. Protein phosphatase 2A (PP2A) is a serine and threonine phosphatase that modulates cell metabolism and cell survival. This study investigated whether melatonin modulates PP2A subunit B in focal cerebral ischemia and glutamate toxicity-induced neuronal cell death in a rat model. Middle cerebral artery occlusion (MCAO) was performed to induce permanent cerebral ischemic injury. Adult male rats were treated with vehicle or melatonin (5 mg/kg) prior to MCAO, and cerebral cortex tissues were collected 24 hr after MCAO. A proteomic approach elucidated the decrease in PP2A subunit B in MCAO-operated animals. Melatonin treatment attenuated injury-induced reductions in PP2A subunit B levels. Western blot analyses indicated that melatonin prevents injury-induced decrease in PP2A subunit B levels. In neuronal cells, glutamate toxicity induced a lowering of PP2A subunit B, while melatonin treatment attenuated the glutamate exposure-induced decreases in PP2A subunit B. These results suggest that the maintenance of PP2A subunit B by melatonin in ischemic injury is critical to the neuroprotective function of melatonin during neuronal cell damage.
褪黑素是一种抗氧化剂，具有缺血性脑损伤的神经保护功能。蛋白磷酸酶 2A（PP2A）是一种丝氨酸和苏氨酸磷酸酶，调节细胞代谢和细胞存活。本研究探讨了褪黑素是否在局灶性脑缺血和谷氨酸毒性诱导的大鼠模型神经元细胞死亡中调节 PP2A 亚基 B。通过大脑中动脉闭塞（MCAO）诱导永久性脑缺血损伤。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。蛋白质组学方法阐明了 MCAO 手术动物中 PP2A 亚基 B 的减少。褪黑素治疗减轻了损伤诱导的 PP2A 亚基 B 水平降低。Western blot 分析表明，褪黑素可防止损伤诱导的 PP2A 亚基 B 水平降低。在神经元细胞中，谷氨酸毒性诱导 PP2A 亚基 B 降低，而褪黑素治疗可减轻谷氨酸暴露诱导的 PP2A 亚基 B 降低。这些结果表明，褪黑素在缺血性损伤中维持 PP2A 亚基 B 对于褪黑素在神经元细胞损伤期间的神经保护功能至关重要。
