Mmunohistochemical Mapping of Total and Hosphorylated Eukaryotic Initiation Factor G in Rat Hippocampus following Global Brain Schemia and Reperfusion

bstract—Partial proteolysis and phosphorylation of the ranslation initiation factor eukaryotic initiation factor 4G eIF4G) occur in reperfused brain, but the contribution of IF4G alterations to brain injury has not been established. A omponent of the complex delivering mRNA to the small ibosomal subunit, eIF4G is also found in stress granules. tress granules sequester inactive 48S preinitiation comlexes during stress-induced translation arrest. We perormed double-labeling immunofluorescence histochemistry or total or ser 1108 phosphorylated eIF4G and the stress ranule component T-cell internal antigen following normohermic, 10 min cardiac arrest-induced global brain ischemia nd up to 4 h reperfusion in the rat. In cornu ammonis (Amon’s horn; CA) 1 at 90 min and 4 h reperfusion, eIF4G taining transformed from a homogeneous to an aggregated istribution. The number of eIF4G-containing stress granules iffered between CA1 and CA3 during reperfusion. In hipocampal pyramidal neurons, phosphorylated eIF4G apeared exclusively in stress granules. Supragranular intereurons of the dentate gyrus showed a large increase in ytoplasmic eIF4G(P) following reperfusion. Immunoblot nalysis with antisera against different portions of eIF4G howed a large increase in phosphorylated C-terminal eIF4G ragments, suggesting these accumulate in the cytoplasm of entate gyrus interneurons. Thus, altered eIF4G subcellular ompartmentalization may contribute to prolonged translaion arrest in CA1 pyramidal neurons. Accumulation of phoshorylated eIF4G fragments may contribute to the vulnerabil-