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Down-regulation of Cl−pump ClP55 subunit induced enhancement of glutamate neurotoxicity in cultured rat hippocampal neurons

Authors
Journal
Brain Research
0006-8993
Publisher
Elsevier
Publication Date
Volume
1130
Identifiers
DOI: 10.1016/j.brainres.2006.10.096
Keywords
  • Intracellular Cl−Concentration
  • Glutamate
  • Akt
  • Clp55
  • Apoptosis
Disciplines
  • Biology

Abstract

Abstract To test whether the increased intracellular Cl − concentration ([Cl −]i) is responsible for the enhanced glutamate toxicity, antisense oligonucleotide of ClP55, a Cl −-ATPase/pump associated protein, was transfected in cultured rat hippocampal neurons. Neuronal [Cl −]i in the antisense oligonucleotide-transfected culture increased to a level 3- to 4-fold higher than that in control. Glutamate exposure (10 μM, 10 min) increased neuronal apoptosis and decreased Akt-pS 473 level in the antisense oligonucleotide-transfected neurons, but not in control or sense oligonucleotide-transfected ones, suggesting the responsibility of elevated [Cl −]i in the enhancement of glutamate neurotoxicity.

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