| First Author | Park JA | Year | 1999 |
| Journal | J Neurochem | Volume | 73 |
| Issue | 2 | Pages | 450-6 |
| PubMed ID | 10428039 | Mgi Jnum | J:56400 |
| Mgi Id | MGI:1340920 | Doi | 10.1046/j.1471-4159.1999.0730450.x |
| Citation | Park JA, et al. (1999) Induction of an immediate early gene egr-1 by zinc through extracellular signal-regulated kinase activation in cortical culture: its role in zinc-induced neuronal death. J Neurochem 73(2):450-6 |
| abstractText | 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. |
