The differential roles of PEA15 phosphorylations in reactive astrogliosis and astroglial apoptosis following status epilepticus. (December 2018)

• Record Type: Journal Article
• Authors: Park, Jin-Young; Kang, Tae-Cheon
• Is Part Of: Neuroscience research. Volume 137(2018)
• Page Start: 11
• Page End: 22
• Publication Date: 2018-12
• Subjects: AKT -- 3CAI -- CAMKII -- Epilepsy -- KN-93 -- Seizure; Neurosciences -- Research -- Periodicals; Neurosciences -- Research -- Japan -- Periodicals; Neurology -- Periodicals; Neurosciences -- Periodicals; Neurosciences -- Recherche -- Périodiques; Neurosciences -- Recherche -- Japon -- Périodiques; Neurosciences -- Research; Japan; Periodicals; 612.8
• DOI: 10.1016/j.neures.2018.02.003
• Languages: English
• ISSNs: 0168-0102

Abstract

Highlights: PEA15-104 phosphorylation was up-regulated in reactive astrocytes following SE. PEA15-S116 phosphorylation was reduced in apoptotic astrocytes. BIM attenuated SE-induced reactive astrogliosis, but PMA aggravated it. Neither BIM nor PMA affected astroglial apoptosis and neuronal death following SE. PEA15 phosphorylation may distinctly regulate reactive astrocytes and apoptosis. Abstract: Up to this day, the roles of PEA15 expression and its phosphorylation in seizure-related events have not been still unclear. In the present study, we found that PEA15 was distinctly phosphorylated in reactive astrocytes and apoptotic astrocytes in the rat hippocampus following LiCl-pilocarpine-induced status epilepticus (SE, a prolonged seizure activity). PEA15-serine (S) 104 phosphorylation was up-regulated in reactive astrocytes following SE, although PEA15 expression and its S116 phosphorylation were unaltered. Bisindolylmaleimide (BIM), a protein kinase C (PKC) inhibitor, attenuated SE-induced reactive astrogliosis, but phorbol 12-myristate 13-acetate (PMA, a PKC activator) aggravated it. Unlike reactive astrocytes, PEA15-S116 phosphorylation was reduced in apoptotic astrocytes. However, PEA15 expression and its S104 phosphorylation were unchanged in apoptotic astrocyte. Neither BIM nor PMA affected SE-induced astroglial apoptosis. PEA15 expression and its phosphorylations were not relevant to SE-induced CA1 neuronal death. These findings indicate that PEA15-S104 and S116 phosphorylations may play a role in reactive astrogliosis and prevention of astroglial apoptosis, respectively. Therefore, we suggest that the selective manipulation of PEA15 phosphorylations may regulate apoptotic and/or proliferative signals in astrocytes.