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Melatonin prevents down-regulation of astrocytic phosphoprotein PEA-15 in ischemic brain injury


  • Phil-Ok Koh

    1. Department of Anatomy, College of Veterinary Medicine and Research Institute of Life Science, Gyeongsang National University, Jinju, South Korea
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Address reprint requests to Phil-Ok Koh, Department of Anatomy, College of Veterinary Medicine, Gyeongsang National University, 900 Gajwa-dong, Jinju 660-701, South Korea.


Abstract:  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.