Diminished calcium homeostasis and increased susceptibility to excitotoxicity of JS 3/16 progenitor cells after differentiation to oligodendroglia

Takayuki Ito, Usha R. Reddy, Janet L. Stern, Mei Chen, Aki Itoh, David E Pleasure

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

JS 3/16, derived from passaged oligodendroglial cultures prepared from rat cerebral white matter, differentiate from progenitors (OP) into complex process-bearing, galactocerebroside-positive but myelin basic protein-negative immature oligo-dendrocyte-like cells (ImO) after withdrawal of trophic factors. We found that JS 3/16 ImO are markedly more susceptible than OP to cell death after sustained α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate glutamate receptor (AMPA-GluR) activation. This excitotoxicity is preceded by loss of intracellular Ca2+ homeostasis, which is more marked in ImO than OP. We identified three factors likely to contribute to the diminished Ca2+ homeostatic capacity of ImO. First, signal intensities of immunoreactive GluR2, GluR3, and GluR4 AMPA-GluR subunits are increased 1.3- to 2.2-fold in ImO over OP without comparable changes in RNA editing and alternative splicing. Second, transcriptional levels of genes encoding Na+-Ca2+ exchanger proteins and a plasma membrane ATPase (PMCA1), which are necessary for Ca2+ extrusion across the plasma membrane, are lower in ImO than in OP. Third, ImO have more depolarized basal mitochondrial membrane potential (ΔΨ) than OP, and ΔΨ collapses within 15 min after onset of AMPA-GluR activation in almost all ImO, but not in the majority of OP. This ΔΨ collapse limits the capacity of ImO mitochondria to buffer the rise in intracellular Ca2+ caused by AMPA-GluR activation. The JS 3/16 line provides a valuable system for analysis of intracellular Ca2+ homeostasis and AMPA-GluR-mediated excitotoxicity in the oligodendroglial lineage. (C) 2000 Wiley-Liss, Inc.

Original languageEnglish (US)
Pages (from-to)165-180
Number of pages16
JournalGLIA
Volume31
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

Keywords

  • AMPA-glutamate receptor
  • Calcium
  • Cell line
  • Mitochondria
  • Na-Ca exchanger

ASJC Scopus subject areas

  • Immunology

Fingerprint Dive into the research topics of 'Diminished calcium homeostasis and increased susceptibility to excitotoxicity of JS 3/16 progenitor cells after differentiation to oligodendroglia'. Together they form a unique fingerprint.

  • Cite this