Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity

Akira Yoshioka, Yuko Shimizu, Genjiro Hirose, Hiroshi Kitasato, David E Pleasure

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Previously, we have demonstrated that cells of the oligodendroglial lineage express non-NMDA glutamate receptor genes and are damaged by kainate- induced Ca2+ influx via non-NMDA glutamate receptor channels, representing oligodendroglial excitotoxicity. We find in the present study that agents that elevate intracellular cyclic AMP prevent oligodendroglial excitotoxicity. After oligodendrocyte-like cells, differentiated from the CG- 4 cell line established from rat oligodendrocyte type-2 astrocyte progenitor cells, were exposed to 2 mM kainate for 24 h, cell death was evaluated by measuring activity of lactate dehydrogenase released into the culture medium. Released lactate dehydrogenase increased about threefold when exposed to 2 mM kainate. Kainate-induced cell death was prevented by one of the following agents: adenylate cyclase activator (forskolin), cyclic AMP analogues (dibutyryl cyclic AMP and 8-bromo-cyclic AMP), and cyclic AMP phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, pentoxifylline, propentofylline, and ibudilast). Simultaneous addition of both forskolin and phosphodiesterase inhibitors prevented the kainate-induced cell death in an additive manner. A remarkable increase in Ca2+ influx (~5.5-fold) also was induced by kainate. The cyclic AMP-elevating agents caused a partial suppression of the kainate-induced increase in Ca2+ influx, leading to a less prominent response of intracellular Ca2+ concentration to kainate. The suppressing effect of forskolin on the kainate-induced Ca2+ influx was partially reversed by H-89, an inhibitor of cyclic AMP-dependent protein kinase. In contrast to this, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, brought about a decrease in the kainate-induced Ca2+ influx. We therefore concluded that cyclic AMP-elevating agents prevented oligodendroglial excitotoxicity by cyclic AMP-dependent protein kinase- dependent protein phosphorylation, resulting in decreased kainate-induced Ca2+ influx.

Original languageEnglish (US)
Pages (from-to)2416-2423
Number of pages8
JournalJournal of Neurochemistry
Volume70
Issue number6
StatePublished - Jun 1998
Externally publishedYes

Fingerprint

Kainic Acid
Cyclic AMP
Colforsin
Cell death
Cell Death
Phosphodiesterase Inhibitors
Oligodendroglia
Glutamate Receptors
L-Lactate Dehydrogenase
8-Bromo Cyclic Adenosine Monophosphate
1-Methyl-3-isobutylxanthine
Protein Phosphatase 2
Pentoxifylline
Okadaic Acid
Bucladesine
Phosphorylation
Cell Lineage
Cyclic AMP-Dependent Protein Kinases
Adenylyl Cyclases
Astrocytes

Keywords

  • Ca influx
  • Cyclic AMP
  • Cyclic AMP-dependent protein kinase
  • Non-NMDA glutamate receptors
  • Oligodendroglia
  • Protein phosphatase

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Yoshioka, A., Shimizu, Y., Hirose, G., Kitasato, H., & Pleasure, D. E. (1998). Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity. Journal of Neurochemistry, 70(6), 2416-2423.

Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity. / Yoshioka, Akira; Shimizu, Yuko; Hirose, Genjiro; Kitasato, Hiroshi; Pleasure, David E.

In: Journal of Neurochemistry, Vol. 70, No. 6, 06.1998, p. 2416-2423.

Research output: Contribution to journalArticle

Yoshioka, A, Shimizu, Y, Hirose, G, Kitasato, H & Pleasure, DE 1998, 'Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity', Journal of Neurochemistry, vol. 70, no. 6, pp. 2416-2423.
Yoshioka A, Shimizu Y, Hirose G, Kitasato H, Pleasure DE. Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity. Journal of Neurochemistry. 1998 Jun;70(6):2416-2423.
Yoshioka, Akira ; Shimizu, Yuko ; Hirose, Genjiro ; Kitasato, Hiroshi ; Pleasure, David E. / Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity. In: Journal of Neurochemistry. 1998 ; Vol. 70, No. 6. pp. 2416-2423.
@article{d5d30dfd35e04420a6248fdb96e75c3f,
title = "Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity",
abstract = "Previously, we have demonstrated that cells of the oligodendroglial lineage express non-NMDA glutamate receptor genes and are damaged by kainate- induced Ca2+ influx via non-NMDA glutamate receptor channels, representing oligodendroglial excitotoxicity. We find in the present study that agents that elevate intracellular cyclic AMP prevent oligodendroglial excitotoxicity. After oligodendrocyte-like cells, differentiated from the CG- 4 cell line established from rat oligodendrocyte type-2 astrocyte progenitor cells, were exposed to 2 mM kainate for 24 h, cell death was evaluated by measuring activity of lactate dehydrogenase released into the culture medium. Released lactate dehydrogenase increased about threefold when exposed to 2 mM kainate. Kainate-induced cell death was prevented by one of the following agents: adenylate cyclase activator (forskolin), cyclic AMP analogues (dibutyryl cyclic AMP and 8-bromo-cyclic AMP), and cyclic AMP phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, pentoxifylline, propentofylline, and ibudilast). Simultaneous addition of both forskolin and phosphodiesterase inhibitors prevented the kainate-induced cell death in an additive manner. A remarkable increase in Ca2+ influx (~5.5-fold) also was induced by kainate. The cyclic AMP-elevating agents caused a partial suppression of the kainate-induced increase in Ca2+ influx, leading to a less prominent response of intracellular Ca2+ concentration to kainate. The suppressing effect of forskolin on the kainate-induced Ca2+ influx was partially reversed by H-89, an inhibitor of cyclic AMP-dependent protein kinase. In contrast to this, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, brought about a decrease in the kainate-induced Ca2+ influx. We therefore concluded that cyclic AMP-elevating agents prevented oligodendroglial excitotoxicity by cyclic AMP-dependent protein kinase- dependent protein phosphorylation, resulting in decreased kainate-induced Ca2+ influx.",
keywords = "Ca influx, Cyclic AMP, Cyclic AMP-dependent protein kinase, Non-NMDA glutamate receptors, Oligodendroglia, Protein phosphatase",
author = "Akira Yoshioka and Yuko Shimizu and Genjiro Hirose and Hiroshi Kitasato and Pleasure, {David E}",
year = "1998",
month = "6",
language = "English (US)",
volume = "70",
pages = "2416--2423",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "6",

}

TY - JOUR

T1 - Cyclic AMP-elevating agents prevent oligodendroglial excitotoxicity

AU - Yoshioka, Akira

AU - Shimizu, Yuko

AU - Hirose, Genjiro

AU - Kitasato, Hiroshi

AU - Pleasure, David E

PY - 1998/6

Y1 - 1998/6

N2 - Previously, we have demonstrated that cells of the oligodendroglial lineage express non-NMDA glutamate receptor genes and are damaged by kainate- induced Ca2+ influx via non-NMDA glutamate receptor channels, representing oligodendroglial excitotoxicity. We find in the present study that agents that elevate intracellular cyclic AMP prevent oligodendroglial excitotoxicity. After oligodendrocyte-like cells, differentiated from the CG- 4 cell line established from rat oligodendrocyte type-2 astrocyte progenitor cells, were exposed to 2 mM kainate for 24 h, cell death was evaluated by measuring activity of lactate dehydrogenase released into the culture medium. Released lactate dehydrogenase increased about threefold when exposed to 2 mM kainate. Kainate-induced cell death was prevented by one of the following agents: adenylate cyclase activator (forskolin), cyclic AMP analogues (dibutyryl cyclic AMP and 8-bromo-cyclic AMP), and cyclic AMP phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, pentoxifylline, propentofylline, and ibudilast). Simultaneous addition of both forskolin and phosphodiesterase inhibitors prevented the kainate-induced cell death in an additive manner. A remarkable increase in Ca2+ influx (~5.5-fold) also was induced by kainate. The cyclic AMP-elevating agents caused a partial suppression of the kainate-induced increase in Ca2+ influx, leading to a less prominent response of intracellular Ca2+ concentration to kainate. The suppressing effect of forskolin on the kainate-induced Ca2+ influx was partially reversed by H-89, an inhibitor of cyclic AMP-dependent protein kinase. In contrast to this, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, brought about a decrease in the kainate-induced Ca2+ influx. We therefore concluded that cyclic AMP-elevating agents prevented oligodendroglial excitotoxicity by cyclic AMP-dependent protein kinase- dependent protein phosphorylation, resulting in decreased kainate-induced Ca2+ influx.

AB - Previously, we have demonstrated that cells of the oligodendroglial lineage express non-NMDA glutamate receptor genes and are damaged by kainate- induced Ca2+ influx via non-NMDA glutamate receptor channels, representing oligodendroglial excitotoxicity. We find in the present study that agents that elevate intracellular cyclic AMP prevent oligodendroglial excitotoxicity. After oligodendrocyte-like cells, differentiated from the CG- 4 cell line established from rat oligodendrocyte type-2 astrocyte progenitor cells, were exposed to 2 mM kainate for 24 h, cell death was evaluated by measuring activity of lactate dehydrogenase released into the culture medium. Released lactate dehydrogenase increased about threefold when exposed to 2 mM kainate. Kainate-induced cell death was prevented by one of the following agents: adenylate cyclase activator (forskolin), cyclic AMP analogues (dibutyryl cyclic AMP and 8-bromo-cyclic AMP), and cyclic AMP phosphodiesterase inhibitors (3-isobutyl-1-methylxanthine, pentoxifylline, propentofylline, and ibudilast). Simultaneous addition of both forskolin and phosphodiesterase inhibitors prevented the kainate-induced cell death in an additive manner. A remarkable increase in Ca2+ influx (~5.5-fold) also was induced by kainate. The cyclic AMP-elevating agents caused a partial suppression of the kainate-induced increase in Ca2+ influx, leading to a less prominent response of intracellular Ca2+ concentration to kainate. The suppressing effect of forskolin on the kainate-induced Ca2+ influx was partially reversed by H-89, an inhibitor of cyclic AMP-dependent protein kinase. In contrast to this, okadaic acid, an inhibitor of protein phosphatases 1 and 2A, brought about a decrease in the kainate-induced Ca2+ influx. We therefore concluded that cyclic AMP-elevating agents prevented oligodendroglial excitotoxicity by cyclic AMP-dependent protein kinase- dependent protein phosphorylation, resulting in decreased kainate-induced Ca2+ influx.

KW - Ca influx

KW - Cyclic AMP

KW - Cyclic AMP-dependent protein kinase

KW - Non-NMDA glutamate receptors

KW - Oligodendroglia

KW - Protein phosphatase

UR - http://www.scopus.com/inward/record.url?scp=0031800045&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031800045&partnerID=8YFLogxK

M3 - Article

C2 - 9603206

AN - SCOPUS:0031800045

VL - 70

SP - 2416

EP - 2423

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 6

ER -