Premium
Melatonin prevents down‐regulation of astrocytic phosphoprotein PEA‐15 in ischemic brain injury
Author(s) -
Koh PhilOk
Publication year - 2011
Publication title -
journal of pineal research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.881
H-Index - 131
eISSN - 1600-079X
pISSN - 0742-3098
DOI - 10.1111/j.1600-079x.2011.00900.x
Subject(s) - melatonin , neuroprotection , glutamate receptor , phosphoprotein , free radical scavenger , western blot , biology , apoptosis , pharmacology , pea protein , endocrinology , medicine , biochemistry , phosphorylation , oxidative stress , receptor , gene
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.