α- amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage

Akira Yoshioka, Mattie Hardy, Donald P. Younkin, Judith B. Grinspan, Janet L. Stern, David E Pleasure

Research output: Contribution to journalArticle

127 Citations (Scopus)

Abstract

We demonstrate by reverse transcriptase-polymerase chain reaction and Southern blotting that an immortalized rat oligodendroglial cell line (CG-4) expresses the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized cells of the rat oligodendroglial lineage express the GluR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that both immortalized and nonimmortalized cells of the oligodendroglial lineage are damaged by a 24-h exposure to 500 μM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 m/W α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitro-quinoxaline-2,3-dione and is also averted if Ca2+ is removed from the culture medium. Cyclothiazide, which blocks desensitization of AMPA-preferring GluRs, increases cytotoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AMPA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca2+-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

Original languageEnglish (US)
Pages (from-to)2442-2448
Number of pages7
JournalJournal of Neurochemistry
Volume64
Issue number6
StatePublished - Jun 1995
Externally publishedYes

Fingerprint

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
AMPA Receptors
Kainic Acid
Glutamate Receptors
D-Aspartic Acid
Cell Lineage
Cytotoxicity
Rats
Genes
Cells
Quinoxalines
Polymerase chain reaction
RNA-Directed DNA Polymerase
Southern Blotting
Reverse Transcriptase Polymerase Chain Reaction
Toxicity
Culture Media
Glutamic Acid
Assays
Oxidoreductases

Keywords

  • Cyclothiazide
  • Excitotoxicity
  • Kainate
  • Non-NMDA glutamate receptors
  • O-2A cells
  • Oligodendroglia

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

α- amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage. / Yoshioka, Akira; Hardy, Mattie; Younkin, Donald P.; Grinspan, Judith B.; Stern, Janet L.; Pleasure, David E.

In: Journal of Neurochemistry, Vol. 64, No. 6, 06.1995, p. 2442-2448.

Research output: Contribution to journalArticle

Yoshioka, Akira ; Hardy, Mattie ; Younkin, Donald P. ; Grinspan, Judith B. ; Stern, Janet L. ; Pleasure, David E. / α- amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors mediate excitotoxicity in the oligodendroglial lineage. In: Journal of Neurochemistry. 1995 ; Vol. 64, No. 6. pp. 2442-2448.
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AU - Yoshioka, Akira

AU - Hardy, Mattie

AU - Younkin, Donald P.

AU - Grinspan, Judith B.

AU - Stern, Janet L.

AU - Pleasure, David E

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N2 - We demonstrate by reverse transcriptase-polymerase chain reaction and Southern blotting that an immortalized rat oligodendroglial cell line (CG-4) expresses the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized cells of the rat oligodendroglial lineage express the GluR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that both immortalized and nonimmortalized cells of the oligodendroglial lineage are damaged by a 24-h exposure to 500 μM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 m/W α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitro-quinoxaline-2,3-dione and is also averted if Ca2+ is removed from the culture medium. Cyclothiazide, which blocks desensitization of AMPA-preferring GluRs, increases cytotoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AMPA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca2+-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

AB - We demonstrate by reverse transcriptase-polymerase chain reaction and Southern blotting that an immortalized rat oligodendroglial cell line (CG-4) expresses the non-N-methyl-D-aspartate (non-NMDA) glutamate receptor (GluR) genes GluR2-7, KA-1, and KA-2 and that nonimmortalized cells of the rat oligodendroglial lineage express the GluR1-3, GluR5-7, KA-1, and KA-2 genes. Lactic dehydrogenase release assays show that both immortalized and nonimmortalized cells of the oligodendroglial lineage are damaged by a 24-h exposure to 500 μM kainate or 5 mM L-glutamate, but not by a 24-h exposure to up to 10 m/W α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA). Damage is prevented by the non-NMDA GluR channel inhibitor 6-cyano-7-nitro-quinoxaline-2,3-dione and is also averted if Ca2+ is removed from the culture medium. Cyclothiazide, which blocks desensitization of AMPA-preferring GluRs, increases cytotoxicity of kainate as well as inducing toxicity of AMPA. We conclude that cells of the oligodendroglial lineage express a population of AMPA-preferring and possibly also kainate-preferring GluR channels that are capable of mediating Ca2+-dependent excitotoxicity and that AMPA-induced cytotoxicity is blocked by desensitization of AMPA-preferring GluRs.

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