NEUROCHEMISTRYNuclear translocation of extracellular signal-regulated kinases in neuronal excitotoxicityJiang, Qian; Gu, Zhenglin; Zhang, GuangyiCA Author Information Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, PR China CACorresponding Author Received 10 May 2001; accepted 28 May 2001 Neuroreport: August 8, 2001 - Volume 12 - Issue 11 - p 2417-2421 Buy Abstract Subcellular distributions of extracellular signal-kinases (ERK1/2), including their activated form (p-ERK1/2), were investigated in glutamate-induced apoptotic-like death in cultured rat cortical neurons by Western immunoblot and immunocytochemistry. During 15 min glutamate exposure, p-ERK1/2 was increased in both cytosol and nuclear extracts, but prominently so in nuclear extracts. Simultaneously, ERK1/2 were mildly decreased in cytosol (to 0.7-fold vs sham control), largely increased in nuclear extracts (to 6.2-fold vs sham control), but not changed in total cell extracts. Immunocytochemistry studies also showed a large increase in nuclear and a mild decrease in cytosol extracts of ERK1/2 at 15 min of exposure. After glutamate exposure, all the above changes reverted simultaneously. The nuclear increase of ERK1/2 was largely prevented by inhibition of ERK1/2 activation, but prolonged by elongation of ERK1/2 activation. These observations suggest that stimulation of glutamate receptors in cortical neurons may incur an activation-dependent transient nuclear translocation of ERK1/2, which might be involved in excitotoxicity through a simultaneous strong elevation of p-ERK1/2 in nucleus. © 2001 Lippincott Williams & Wilkins, Inc.
