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Induction of an Immediate Early Gene egr‐1 by Zinc Through Extracellular Signal‐Regulated Kinase Activation in Cortical Culture
Author(s) -
Park Jeong Ae,
Koh JaeYoung
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0730450.x
Subject(s) - mapk/erk pathway , kinase , microbiology and biotechnology , extracellular , ionomycin , protein kinase a , signal transduction , neurotoxicity , chemistry , biology , intracellular , toxicity , organic chemistry
: Egr‐1 is one of the immediate early transcription factors that are induced after brain insults. However, the mechanism and the role of Egr‐1 induction are not yet determined. In the present study, using mouse cortical cultures, we examined the ionic mechanism of Egr‐1 induction and its role in neuronal death. Although zinc, NMDA, or ionomycin induced comparable neuronal death in cortical culture, only zinc increased Egr‐1 expression, which was attenuated by blocking zinc influx. It is intriguing that brief exposure to zinc induced sustained extracellular signal‐regulated kinase (Erk) activation. PD098059, an inhibitor of the Erk 1/2 upstream kinase mitogen‐activated protein kinase kinase 1 (MEK1), blocked Erk 1/2 activation, Egr‐1 induction, and neuronal death by zinc. The present study has demonstrated that zinc, rather than calcium, induces lasting Egr‐1 expression in cortical culture by activating Erk 1/2, which is part of a cascade that may play an active role in zinc neurotoxicity. We propose that translocation of endogenous zinc may be the key mechanism of Egr‐1 induction and neuronal death in brain ischemia.