PMID- 30143487
OWN - NLM
STAT- MEDLINE
DCOM- 20181116
LR  - 20181202
IS  - 1550-8080 (Electronic)
IS  - 0091-7370 (Linking)
VI  - 48
IP  - 4
DP  - 2018 Jul
TI  - Disruption of GluR2/GAPDH Complex Interaction by TAT-GluR2(NT1-3-2) Peptide 
      Protects against Neuronal Death Induced by Epilepsy.
PG  - 460-468
AB  - OBJECTIVE: Excitotoxic neuronal death induced by epilepsy is associated with 
      alpha-amino-3-hydroxyl-5-methylisoxazole-4-propionate acid (AMPA) receptors. The 
      GluR2 subunit of AMPA receptors (AMPARs) may bind with glyceraldehyde-3-phosphate 
      dehydrogenase (GAPDH). The GluR2/GAPDH complex co-internalizes upon stimulation 
      of AMPARs, which might be involved in the development of epilepsy. In this 
      research, we hypothesized that disruption of the GluR2/GAPDH interaction with an 
      interfering peptide would protect against neuronal damage in vivo. METHODS: Rat 
      models of epilepsy were induced by pilocarpine hydrochloride. TAT-GluR2(NT1-3-2) 
      peptide was synthesized to block interaction between GluR2 and GAPDH. Fluoro-Jade 
      B and TUNEL staining were used to detect degeneration and apoptosis of neurons 
      after interference by the peptide. Co-immunoprecipitation assay and western-blot 
      was performed to confirm that the peptide disturbed interactions between GluR2 
      and GAPDH. RESULTS: The time of epileptic seizure was found to be delayed after 
      peptide interference. It was concluded that administration of an interfering 
      peptide is able to significantly reduce degeneration and apoptosis of neurons. 
      The GluR2/GAPDH interaction and GAPDH nuclear expression were upregulated in the 
      hippocampus of rats subjected to pilocarpine-induced seizures. CONCLUSION: 
      Disruption of the GluR2/GAPDH interaction by administration of an interfering 
      peptide protects against seizure-induced neuronal damage that is dose dependent. 
      Thus, the GluR2/GAPDH interaction may be a novel therapeutic target for 
      development of treatment for epilepsy.
CI  - (c) 2018 by the Association of Clinical Scientists, Inc.
FAU - Mi, Qing
AU  - Mi Q
AD  - Department of Pediatrics, Qilu Hospital of Shandong University.
AD  - Department of Pediatrics, Taian City Central Hospital.
FAU - Yao, Guo
AU  - Yao G
AD  - Department of Pediatrics, Taian City Central Hospital.
FAU - Zhang, Guang You
AU  - Zhang GY
AD  - Department of Pediatrics, Taian City Central Hospital.
FAU - Zhang, Jinghui
AU  - Zhang J
AD  - Department of Pediatrics, Qilu Hospital of Shandong University.
FAU - Wang, Jiwen
AU  - Wang J
AD  - Department of Pediatrics, Qilu Hospital of Shandong University 
      miqng_arti_mit@163.com.
AD  - Department of Neurology, Shanghai Children's Medical Center, Shanghai, China.
FAU - Zhao, Peng
AU  - Zhao P
AD  - Department of Pediatrics, Taian City Central Hospital.
FAU - Liu, Jing
AU  - Liu J
AD  - Department of Pediatrics, Taian City Central Hospital.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Ann Clin Lab Sci
JT  - Annals of clinical and laboratory science
JID - 0410247
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Peptides)
RN  - 0 (Receptors, AMPA)
RN  - 0 (tat Gene Products, Human Immunodeficiency Virus)
RN  - 01MI4Q9DI3 (Pilocarpine)
RN  - EC 1.2.1.12 (Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating))
RN  - P6W5IXV8V9 (glutamate receptor ionotropic, AMPA 2)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Death/drug effects
MH  - Cell Nucleus/drug effects/metabolism
MH  - Epilepsy/chemically induced/*drug therapy/*pathology
MH  - Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/*metabolism
MH  - Hippocampus/drug effects/pathology
MH  - Male
MH  - Nerve Degeneration/drug therapy/pathology
MH  - Neurons/drug effects/metabolism/*pathology
MH  - Neuroprotective Agents/pharmacology/*therapeutic use
MH  - Peptides/chemical synthesis/chemistry/pharmacology/*therapeutic use
MH  - Pilocarpine
MH  - Protein Transport/drug effects
MH  - Rats, Wistar
MH  - Receptors, AMPA/*metabolism
MH  - tat Gene Products, Human Immunodeficiency 
      Virus/chemistry/pharmacology/*therapeutic use
OTO - NOTNLM
OT  - GAPDH
OT  - GluR2
OT  - GluR2NT1-3-2 peptide
OT  - epilepsy
EDAT- 2018/08/26 06:00
MHDA- 2018/11/18 06:00
CRDT- 2018/08/26 06:00
PHST- 2018/08/26 06:00 [entrez]
PHST- 2018/08/26 06:00 [pubmed]
PHST- 2018/11/18 06:00 [medline]
AID - 48/4/460 [pii]
PST - ppublish
SO  - Ann Clin Lab Sci. 2018 Jul;48(4):460-468.