RGD Reference Report - Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain. - Rat Genome Database

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Endoplasmic reticulum stress inhibition protects against excitotoxic neuronal injury in the rat brain.

Authors: Sokka, AL  Putkonen, N  Mudo, G  Pryazhnikov, E  Reijonen, S  Khiroug, L  Belluardo, N  Lindholm, D  Korhonen, L 
Citation: Sokka AL, etal., J Neurosci. 2007 Jan 24;27(4):901-8.
RGD ID: 10755427
Pubmed: PMID:17251432   (View Abstract at PubMed)
PMCID: PMC6672923   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.4289-06.2007   (Journal Full-text)

Elevated brain glutamate with activation of neuronal glutamate receptors accompanies neurological disorders, such as epilepsy and brain trauma. However, the mechanisms by which excitotoxicity triggers neuronal injury are not fully understood. We have studied the glutamate receptor agonist kainic acid (KA) inducing seizures and excitotoxic cell death. KA caused the disintegration of the endoplasmic reticulum (ER) membrane in hippocampal neurons and ER stress with the activation of the ER proteins Bip, Chop, and caspase-12. Salubrinal, inhibiting eIF2alpha (eukaryotic translation initiation factor 2 subunit alpha) dephosphorylation, significantly reduced KA-induced ER stress and neuronal death in vivo and in vitro. KA-induced rise in intracellular calcium was not affected by Salubrinal. The results show that ER responses are essential parts of excitotoxicity mediated by glutamate receptor activation and that Salubrinal decreases neuronal death in vivo. Inhibition of ER stress by small molecular compounds may be beneficial for treatment of various neuronal injuries and brain disorders.



Gene-Chemical Interaction Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
EIF2S1Humankainic acid increases phosphorylationISOEif2s1 (Rattus norvegicus)kainic acid increases phosphorylation of Eif2s1 in rat neuronsRGD 
Eif2s1Ratkainic acid increases phosphorylationEXP kainic acid increases phosphorylation of Eif2s1 in rat neuronsRGD 
Eif2s1Mousekainic acid increases phosphorylationISOEif2s1 (Rattus norvegicus)kainic acid increases phosphorylation of Eif2s1 in rat neuronsRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Casp12Ratresponse to kainic acid  IEP  RGD 
Ddit3Ratresponse to kainic acid  IEP  RGD 
Eif2s1Ratresponse to kainic acid  IEP  RGD 
Gdf10Ratresponse to kainic acid  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Casp12  (caspase 12)
Ddit3  (DNA-damage inducible transcript 3)
Eif2s1  (eukaryotic translation initiation factor 2 subunit alpha)
Gdf10  (growth differentiation factor 10)

Genes (Mus musculus)
Eif2s1  (eukaryotic translation initiation factor 2, subunit 1 alpha)

Genes (Homo sapiens)
EIF2S1  (eukaryotic translation initiation factor 2 subunit alpha)


Additional Information