Following hypoglycemic injury to rat pheochromocytoma PC12 cells, cells display nuclear chromatin condensation and nucleosome-sized DNA fragmentation. Electrophoretic mobility shift assays were used to characterize binding of nuclear proteins to consensus sequences for AP-1, nuclear factor kappa B (NF kappa B), and octamer family after glucose deprivation. While AP-1 DNA binding activity and NF kappa B DNA binding activity were transiently stimulated, DNA binding to the octamer motif decreased. These data suggest that changes in nuclear protein binding to specific consensus sequences are an early molecular event in hypoglycemic-ischemic injury-induced neuronal cell death.