RGD Reference Report - Effect of brain ischemia and reperfusion on the localization of phosphorylated eukaryotic initiation factor 2 alpha. - Rat Genome Database

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Effect of brain ischemia and reperfusion on the localization of phosphorylated eukaryotic initiation factor 2 alpha.

Authors: Degracia, DJ  Sullivan, JM  Neumar, RW  Alousi, SS  Hikade, KR  Pittman, JE  White, BC  Rafols, JA  Krause, GS 
Citation: DeGracia DJ, etal., J Cereb Blood Flow Metab. 1997 Dec;17(12):1291-302.
RGD ID: 10395349
Pubmed: (View Article at PubMed) PMID:9397028
DOI: Full-text: DOI:10.1097/00004647-199712000-00004

Postischemic brain reperfusion is associated with a substantial and long-lasting reduction of protein synthesis in selectively vulnerable neurons. Because the overall translation initiation rate is typically regulated by altering the phosphorylation of serine 51 on the alpha-subunit of eukaryotic initiation factor 2 (eIF-2 alpha), we used an antibody specific to phosphorylated eIF-2 alpha [eIF-2(alpha P)] to study the regional and cellular distribution of eIF-2(alpha P) in normal, ischemic, and reperfused rat brains. Western blots of brain postmitochondrial supernatants revealed that approximately 1% of all eIF-2 alpha is phosphorylated in controls, eIF-2(alpha P) is not reduced by up to 30 minutes of ischemia, and eIF-2(alpha P) is increased approximately 20-fold after 10 and 90 minutes of reperfusion. Immunohistochemistry shows localization of eIF-2(alpha P) to astrocytes in normal brains, a massive increase in eIF-2(alpha P) in the cytoplasm of neurons within the first 10 minutes of reperfusion, accumulation of eIF-2(alpha P) in the nuclei of selectively vulnerable neurons after 1 hour of reperfusion, and morphology suggesting pyknosis or apoptosis in neuronal nuclei that continue to display eIF-2(alpha P) after 4 hours of reperfusion. These observations, together with the fact that eIF-2(alpha P) inhibits translation initiation, make a compelling case that eIF-2(alpha P) is responsible for reperfusion-induced inhibition of protein synthesis in vulnerable neurons.

Gene Ontology Annotations    

Cellular Component

Objects Annotated

Genes (Rattus norvegicus)
Eif2s1  (eukaryotic translation initiation factor 2 subunit alpha)

Additional Information