An enhanced expression of the immediate early gene, Egr-1, is associated with neuronal apoptosis in culture

M. V. Catania, A. Copani, A. Calogero, G. I. Ragonese, D. F. Condorelli, F. Nicoletti

Research output: Contribution to journalArticlepeer-review

Abstract

Cultured cerebellar granule cells grown in medium containing 10 mM K+ (K10) underwent apoptosis after four to five days in vitro, unless they were rescued by the addition of insulin-like growth factor-I. The few GABAergic neurons present in the cultures were more resistant to apoptotic degeneration, as indicated by double fluorescent staining with the chromatin dye Hoechst 33258 and with glutamate decarboxylase-67 antibodies. As compared with sister cultures grown in 25 mM K+, K10 cultures showed an increased expression of the Egr-1 protein and a reduced expression of the Fos protein. The increase in Egr-1 was more substantial in granule cells than in GABAergic neurons, and was not observed in K10 cultures chronically exposed to insulin- like growth factor-I. To examine the temporal relationship between the increase in Egr-1 and the development of programmed cell death, we induced apoptosis in K25 cultures at six days in vitro by replacing their medium with serum-free K10 medium. A substantial, but transient, increase in Egr-1 expression was observed in granule cells 6 h after switching the medium, a time that preceded the appearance of the phoenotypical markers of apoptotic death. An early reduction in the Fos protein was observed after switching the medium from K25 into serum-free K10, but also after switching the medium into serum-free K25, a condition which was not associated with the development of apoptosis nor with the increase in Egr-1. We suggest that a transient induction of Egr-1 contributes to the chain of events leading to the execution phase of neuronal apoptosis in culture.

Original languageEnglish
Pages (from-to)1529-1538
Number of pages10
JournalNeuroscience
Volume91
Issue number4
DOIs
Publication statusPublished - Jul 1999

Keywords

  • Apoptosis
  • Cultured granule cells
  • Egr-1
  • Fos
  • GABAergic neurons

ASJC Scopus subject areas

  • Neuroscience(all)

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