Down-regulation of GluR2 is associated with Ca2+-dependent protease activities in kainate-induced apoptotic cell death in culturd rat hippocampal neurons

Shu Yan Li, Ju Hua Ni, Desheng Xu, Hong Ti Jia

Research output: Contribution to journalArticle

Abstract

In the present study, the molecular mechanisms underlying kainate-induced neurotoxicity were characterized in cultured rat hippocampal neurons. Long-term exposure to kainate caused typically apoptotic cell death, which was accompanied by the accumulation of calcium, marked down-regulation of GluR2 subunit, and the activation of calpain and caspase-3. All these alterations were prevented by alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) receptor antagonist CNQX, but not by NMDA receptor antagonist MK801 and membrane L-type calcium channel antagonist nifedipine. In the presence of cyclothiazide, kainate-induced neurotoxicity was significantly enhanced. Inhibition of either caspases by zVAD-fmk or calpains by calpeptin protected neurons from neurotoxicity. These results suggest that long-term exposure of hippocampal neurons to kainate causes apoptosis, whose mechanisms involve multiple Ca2+-dependent cascades, in which AMPA receptor subunits may be targets for Ca2+-activated protease-mediated degradation during kainate-induced neuron apoptosis.

Original languageEnglish (US)
Pages (from-to)105-108
Number of pages4
JournalNeuroscience Letters
Volume352
Issue number2
DOIs
StatePublished - Dec 11 2003

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Kainic Acid
Peptide Hydrolases
Cell Death
Down-Regulation
Calpain
Neurons
Apoptosis
6-Cyano-7-nitroquinoxaline-2,3-dione
L-Type Calcium Channels
Acids
Calcium Channel Blockers
Nifedipine
Caspases
N-Methyl-D-Aspartate Receptors
Caspase 3
Calcium
Membranes
bucide

Keywords

  • Alpha-Amino-3-hydroxy-5-methylisoxazole-4- proprionic acid receptor
  • Apoptosis
  • Caspase-3
  • GluR2
  • Kainate
  • Neurotoxicity

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Down-regulation of GluR2 is associated with Ca2+-dependent protease activities in kainate-induced apoptotic cell death in culturd rat hippocampal neurons. / Li, Shu Yan; Ni, Ju Hua; Xu, Desheng; Jia, Hong Ti.

In: Neuroscience Letters, Vol. 352, No. 2, 11.12.2003, p. 105-108.

Research output: Contribution to journalArticle

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