PMID- 33348808
OWN - NLM
STAT- MEDLINE
DCOM- 20210318
LR  - 20231213
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 21
IP  - 24
DP  - 2020 Dec 17
TI  - Src/CK2/PTEN-Mediated GluN2B and CREB Dephosphorylations Regulate the 
      Responsiveness to AMPA Receptor Antagonists in Chronic Epilepsy Rats.
LID - 10.3390/ijms21249633 [doi]
LID - 9633
AB  - Both alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptor (AMPAR) and 
      N-methyl-D-aspartate receptor (NMDAR) have been reported as targets for treatment 
      of epilepsy. To investigate the roles and interactions of AMPAR and NMDAR in 
      ictogenesis of epileptic hippocampus, we analyzed AMPAR antagonists (perampanel 
      and GYKI 52466)-mediated phosphatase and tensin homolog deleted on chromosome 10 
      (PTEN) regulation and glutamate ionotropic receptor NMDA type subunit 2B (GluN2B) 
      tyrosine (Y) 1472 phosphorylation in epilepsy rats. Both perampanel and GYKI 
      52466 increased PTEN expression and its activity (reduced phosphorylation), 
      concomitant with decreased activities (phosphorylations) of Src family-casein 
      kinase 2 (CK2) signaling pathway. Compatible with these, they also restored the 
      upregulated GluN2B Y1472 and Ca(2+)/cAMP response element-binding protein (CREB) 
      serine (S) 133 phosphorylations and surface expression of glutamate ionotropic 
      receptor AMPA type subunit 1 (GRIA1) to basal level in the epileptic hippocampus. 
      These effects of perampanel and GYKI 52466 are observed in responders (whose 
      seizure activities are responsive to AMPAR antagonists), but not non-responders 
      (whose seizure activities were uncontrolled by AMPAR antagonists). Therefore, our 
      findings suggest that Src/CK2/PTEN-mediated GluN2B Y1472 and CREB S133 
      regulations may be one of the responsible signaling pathways for the generation 
      of refractory seizures in non-responders to AMPAR antagonists.
FAU - Kim, Ji-Eun
AU  - Kim JE
AD  - Department of Anatomy and Neurobiology, College of Medicine, Hallym University, 
      Chuncheon 24252, Korea.
AD  - Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 
      24252, Korea.
FAU - Lee, Duk-Shin
AU  - Lee DS
AD  - Department of Anatomy and Neurobiology, College of Medicine, Hallym University, 
      Chuncheon 24252, Korea.
AD  - Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 
      24252, Korea.
FAU - Park, Hana
AU  - Park H
AD  - Department of Anatomy and Neurobiology, College of Medicine, Hallym University, 
      Chuncheon 24252, Korea.
AD  - Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 
      24252, Korea.
FAU - Kang, Tae-Cheon
AU  - Kang TC
AD  - Department of Anatomy and Neurobiology, College of Medicine, Hallym University, 
      Chuncheon 24252, Korea.
AD  - Institute of Epilepsy Research, College of Medicine, Hallym University, Chuncheon 
      24252, Korea.
LA  - eng
GR  - HRF-202010-005/Hallym University/
PT  - Journal Article
DEP - 20201217
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Creb1 protein, rat)
RN  - 0 (Cyclic AMP Response Element-Binding Protein)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (NR2B NMDA receptor)
RN  - 0 (Receptors, AMPA)
RN  - 0 (Receptors, N-Methyl-D-Aspartate)
RN  - 102771-26-6 (GYKI 52466)
RN  - 12794-10-4 (Benzodiazepines)
RN  - EC 2.7.10.2 (src-Family Kinases)
RN  - EC 2.7.11.1 (Casein Kinase II)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, rat)
SB  - IM
MH  - Animals
MH  - Benzodiazepines/*pharmacology
MH  - Casein Kinase II/genetics/metabolism
MH  - Cyclic AMP Response Element-Binding Protein/genetics/metabolism
MH  - Epilepsy/chemically induced/*drug therapy/metabolism/pathology
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Gene Expression Regulation/*drug effects
MH  - Male
MH  - PTEN Phosphohydrolase/genetics/metabolism
MH  - Phosphorylation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, AMPA/*antagonists & inhibitors
MH  - Receptors, N-Methyl-D-Aspartate/genetics/metabolism
MH  - Signal Transduction
MH  - src-Family Kinases/genetics/metabolism
PMC - PMC7766850
OTO - NOTNLM
OT  - GRIA1
OT  - GYKI 52466
OT  - NMDA receptor
OT  - NR2B
OT  - hippocampus
OT  - perampanel
OT  - pilocarpine
OT  - refractory seizure
COIS- The authors declare no conflict of interest. The funders had no role in the 
      design of the study; in the collection, analyses, or interpretation of data; in 
      the writing of the manuscript, or in the decision to publish the results.
EDAT- 2020/12/23 06:00
MHDA- 2021/03/19 06:00
PMCR- 2020/12/17
CRDT- 2020/12/22 01:04
PHST- 2020/10/28 00:00 [received]
PHST- 2020/12/11 00:00 [revised]
PHST- 2020/12/12 00:00 [accepted]
PHST- 2020/12/22 01:04 [entrez]
PHST- 2020/12/23 06:00 [pubmed]
PHST- 2021/03/19 06:00 [medline]
PHST- 2020/12/17 00:00 [pmc-release]
AID - ijms21249633 [pii]
AID - ijms-21-09633 [pii]
AID - 10.3390/ijms21249633 [doi]
PST - epublish
SO  - Int J Mol Sci. 2020 Dec 17;21(24):9633. doi: 10.3390/ijms21249633.