Protein ubiquitination in rat brain following hypoglycemic coma

Hypoglycemic coma of 30 min duration selectively damages CA1 pyramidal neurons and the crest of dentate gyrus (DG) granule cells in hippocampus. Here, we show by high-resolution confocal microscopy and biochemical analysis that 30 min of hypoglycemic coma induces the ubiquitination and aggregation of several proteins in rat brain tissues. Protein ubiquitination and aggregation occurred in the CA1 and DG regions as early as the end of 30 min of hypoglycemic coma and lasted until neuronal death in the late recovery period after hypoglycemia. In comparison, the neurons surviving hypoglycemia were less affected. On western blots, ubiquitinated proteins (ubi-proteins) were present mainly in Triton-insoluble pellets, indicating that they are irreversibly aggregated. We conclude that proteins are ubiquitinated and aggregated in neurons after hypoglycemia prior to their death. We hypothesize that protein ubiquitination and aggregation may contribute to neuronal damage after hypoglycemia.