The chemokine growth-related gene product β protects rat cerebellar granule cells from apoptotic cell death through α-amino-3-hydroxy-5-methyl- 4-isoxazolepropionate receptors

Cristina Limatola, Maria Teresa Ciotti, Delio Mercanti, Fabrizio Vacca, Davide Ragozzino, Aldo Giovannelli, Angela Santoni, Fabrizio Eusebi, Ricardo Miledi

Research output: Contribution to journalArticle

Abstract

Cultured cerebellar granule neurons are widely used as a cellular model to study mechanisms of neuronal cell death because they undergo programmed cell death when switched from a culture medium containing 25 mM to one containing 5 mM K+. We have found that the growth-related gene product β (GROβ) partially prevents the K+-depletion-induced cell death, and that the neuroprotective action of GROβ on granule cells is mediated through the α- amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) type of ionotropic glutamate receptors. GROβ-induced survival was suppressed by 6-cyano-7- nitroquinoxaline-2,3-dione, which is a specific antagonist of AMPA/kainate receptors, it was not affected by the inhibitor of N-methyl-D-aspartate receptors, 2-amino-5-phosphonopentanoic acid, and was comparable to the survival of granule cells induced by AMPA (10 μM) treatment. Moreover, GROβ-induced neuroprotection was abolished when granule cells were treated with antisense oligonucleotides specific for the AMPA receptor subunits, which significantly reduced receptor expression, as verified by Western blot analysis with subunit-specific antibodies and by granule cell electrophysiological sensitivity to AMPA. Our data demonstrate that GROβ is neurotrophic for cerebellar granule cells, and that this activity depends on AMPA receptors.

Original languageEnglish
Pages (from-to)6197-6201
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume97
Issue number11
DOIs
Publication statusPublished - May 23 2000

Keywords

  • Apoptosis
  • Cerebellar granule neurons
  • Chemokines
  • Glutamate receptors

ASJC Scopus subject areas

  • Genetics
  • General

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