title: Nuclear translocation of extracellular signal-regulated kinases in neuronal excitotoxicity.
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.
authors.affiliation: Research Center for Biochemistry and Molecular Biology, Xuzhou Medical College, Xuzhou 221002, PR China.
authors.forename: Q
authors.initials: Q
authors.lastname: Jiang
authors.forename: Z
authors.initials: Z
authors.lastname: Gu
authors.forename: G
authors.initials: G
authors.lastname: Zhang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002467:Cell Nucleus / Q000201:enzymology*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D003593:Cytoplasm / Q000201:enzymology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009498:Neurotoxins / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013110:Sphingosine / Q000494:pharmacology; D013449:Sulfonamides; D014638:Vanadates / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D005419:Flavonoids; D007546:Isoquinolines; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D013449:Sulfonamides; D018698:Glutamic Acid; D014638:Vanadates; D016291:Dizocilpine Maleate; D019833:Genistein; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010749:Phosphoprotein Phosphatases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide; D013110:Sphingosine; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one