Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line

Akira Yoshioka, Yoko Yamaya, Shinji Saiki, Masumi Kanemoto, Genjiro Hirose, David E Pleasure

Research output: Contribution to journalArticle

32 Citations (Scopus)

Abstract

Previously, we have demonstrated that excitotoxicity of oligodendrocyte- like cells (OLC), differentiated from immortalized rat O-2A progenitor cells (CG-4 cells), is prevented by cyclic AMP-elevating agents. We now report that some agents that elevate cyclic GMP prevent OLC excitotoxicity. Kainate- induced injury was prevented by cyclic GMP analogues (8-bromo-cyclic GMP and dibutyryl cyclic GMP), a guanylate cyclase activator [atrial natriuretic peptide (ANP)], and phosphodiesterase inhibitors [3-isobutyl-1-methylxanthine (IBMX), ibudilast, propentofylline, and rolipram]. When both forskolin and 8- bromo-cyclic GMP were added, kainate-induced injury was additively prevented. There was a strong positive correlation between suppression of kainate- induced Ca2+ influx and prevention of injury by these chemicals. The measurement of intracellular cyclic AMP and cyclic GMP by radioimmunoassay demonstrated the following: an increase of cyclic GMP with treatment with 8- bromo-cyclic GMP, dibutyryl cyclic GMP, and ANP; an increase of cyclic AMP with treatment with ibudilast and rolipram; and an increase of both cyclic AMP and cyclic GMP with treatment with IBMX and propentofylline. Kainate- induced Ca2+ influx was decreased by 8-(4-chlorophenylthiol)-guanosine- 3',5'-monophosphate, an activator of cyclic GMP-dependent protein kinase (PKG), or okadaic acid, an inhibitor of protein phosphatases 1 and 2A. RT-PCR and western blotting of OLC demonstrated transcription of PKG II gene and translation of PKG 1β mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.

Original languageEnglish (US)
Pages (from-to)633-640
Number of pages8
JournalJournal of Neurochemistry
Volume74
Issue number2
DOIs
StatePublished - 2000
Externally publishedYes

Fingerprint

Cyclic GMP-Dependent Protein Kinases
Cyclic GMP
Kainic Acid
Oligodendroglia
Cells
Cell Line
Cyclic AMP
Dibutyryl Cyclic GMP
Rolipram
Atrial Natriuretic Factor
Wounds and Injuries
Guanosine Monophosphate
1-Methyl-3-isobutylxanthine
Protein Phosphatase 2
Okadaic Acid
Messenger RNA
Phosphodiesterase Inhibitors
Guanosine
Guanylate Cyclase
Protein Biosynthesis

Keywords

  • Ca influx
  • Cyclic GMP
  • Cyclic GMP-dependent protein kinase
  • Non-NMDA glutamate receptors
  • Oligodendroglia
  • Protein phosphatases

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line. / Yoshioka, Akira; Yamaya, Yoko; Saiki, Shinji; Kanemoto, Masumi; Hirose, Genjiro; Pleasure, David E.

In: Journal of Neurochemistry, Vol. 74, No. 2, 2000, p. 633-640.

Research output: Contribution to journalArticle

Yoshioka, Akira ; Yamaya, Yoko ; Saiki, Shinji ; Kanemoto, Masumi ; Hirose, Genjiro ; Pleasure, David E. / Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line. In: Journal of Neurochemistry. 2000 ; Vol. 74, No. 2. pp. 633-640.
@article{a6b7b57d06d9454d9df75cfe5d3df669,
title = "Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line",
abstract = "Previously, we have demonstrated that excitotoxicity of oligodendrocyte- like cells (OLC), differentiated from immortalized rat O-2A progenitor cells (CG-4 cells), is prevented by cyclic AMP-elevating agents. We now report that some agents that elevate cyclic GMP prevent OLC excitotoxicity. Kainate- induced injury was prevented by cyclic GMP analogues (8-bromo-cyclic GMP and dibutyryl cyclic GMP), a guanylate cyclase activator [atrial natriuretic peptide (ANP)], and phosphodiesterase inhibitors [3-isobutyl-1-methylxanthine (IBMX), ibudilast, propentofylline, and rolipram]. When both forskolin and 8- bromo-cyclic GMP were added, kainate-induced injury was additively prevented. There was a strong positive correlation between suppression of kainate- induced Ca2+ influx and prevention of injury by these chemicals. The measurement of intracellular cyclic AMP and cyclic GMP by radioimmunoassay demonstrated the following: an increase of cyclic GMP with treatment with 8- bromo-cyclic GMP, dibutyryl cyclic GMP, and ANP; an increase of cyclic AMP with treatment with ibudilast and rolipram; and an increase of both cyclic AMP and cyclic GMP with treatment with IBMX and propentofylline. Kainate- induced Ca2+ influx was decreased by 8-(4-chlorophenylthiol)-guanosine- 3',5'-monophosphate, an activator of cyclic GMP-dependent protein kinase (PKG), or okadaic acid, an inhibitor of protein phosphatases 1 and 2A. RT-PCR and western blotting of OLC demonstrated transcription of PKG II gene and translation of PKG 1β mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.",
keywords = "Ca influx, Cyclic GMP, Cyclic GMP-dependent protein kinase, Non-NMDA glutamate receptors, Oligodendroglia, Protein phosphatases",
author = "Akira Yoshioka and Yoko Yamaya and Shinji Saiki and Masumi Kanemoto and Genjiro Hirose and Pleasure, {David E}",
year = "2000",
doi = "10.1046/j.1471-4159.2000.740633.x",
language = "English (US)",
volume = "74",
pages = "633--640",
journal = "Journal of Neurochemistry",
issn = "0022-3042",
publisher = "Wiley-Blackwell",
number = "2",

}

TY - JOUR

T1 - Cyclic GMP/cyclic GMP-dependent protein kinase system prevents excitotoxicity in an immortalized oligodendroglial cell line

AU - Yoshioka, Akira

AU - Yamaya, Yoko

AU - Saiki, Shinji

AU - Kanemoto, Masumi

AU - Hirose, Genjiro

AU - Pleasure, David E

PY - 2000

Y1 - 2000

N2 - Previously, we have demonstrated that excitotoxicity of oligodendrocyte- like cells (OLC), differentiated from immortalized rat O-2A progenitor cells (CG-4 cells), is prevented by cyclic AMP-elevating agents. We now report that some agents that elevate cyclic GMP prevent OLC excitotoxicity. Kainate- induced injury was prevented by cyclic GMP analogues (8-bromo-cyclic GMP and dibutyryl cyclic GMP), a guanylate cyclase activator [atrial natriuretic peptide (ANP)], and phosphodiesterase inhibitors [3-isobutyl-1-methylxanthine (IBMX), ibudilast, propentofylline, and rolipram]. When both forskolin and 8- bromo-cyclic GMP were added, kainate-induced injury was additively prevented. There was a strong positive correlation between suppression of kainate- induced Ca2+ influx and prevention of injury by these chemicals. The measurement of intracellular cyclic AMP and cyclic GMP by radioimmunoassay demonstrated the following: an increase of cyclic GMP with treatment with 8- bromo-cyclic GMP, dibutyryl cyclic GMP, and ANP; an increase of cyclic AMP with treatment with ibudilast and rolipram; and an increase of both cyclic AMP and cyclic GMP with treatment with IBMX and propentofylline. Kainate- induced Ca2+ influx was decreased by 8-(4-chlorophenylthiol)-guanosine- 3',5'-monophosphate, an activator of cyclic GMP-dependent protein kinase (PKG), or okadaic acid, an inhibitor of protein phosphatases 1 and 2A. RT-PCR and western blotting of OLC demonstrated transcription of PKG II gene and translation of PKG 1β mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.

AB - Previously, we have demonstrated that excitotoxicity of oligodendrocyte- like cells (OLC), differentiated from immortalized rat O-2A progenitor cells (CG-4 cells), is prevented by cyclic AMP-elevating agents. We now report that some agents that elevate cyclic GMP prevent OLC excitotoxicity. Kainate- induced injury was prevented by cyclic GMP analogues (8-bromo-cyclic GMP and dibutyryl cyclic GMP), a guanylate cyclase activator [atrial natriuretic peptide (ANP)], and phosphodiesterase inhibitors [3-isobutyl-1-methylxanthine (IBMX), ibudilast, propentofylline, and rolipram]. When both forskolin and 8- bromo-cyclic GMP were added, kainate-induced injury was additively prevented. There was a strong positive correlation between suppression of kainate- induced Ca2+ influx and prevention of injury by these chemicals. The measurement of intracellular cyclic AMP and cyclic GMP by radioimmunoassay demonstrated the following: an increase of cyclic GMP with treatment with 8- bromo-cyclic GMP, dibutyryl cyclic GMP, and ANP; an increase of cyclic AMP with treatment with ibudilast and rolipram; and an increase of both cyclic AMP and cyclic GMP with treatment with IBMX and propentofylline. Kainate- induced Ca2+ influx was decreased by 8-(4-chlorophenylthiol)-guanosine- 3',5'-monophosphate, an activator of cyclic GMP-dependent protein kinase (PKG), or okadaic acid, an inhibitor of protein phosphatases 1 and 2A. RT-PCR and western blotting of OLC demonstrated transcription of PKG II gene and translation of PKG 1β mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.

KW - Ca influx

KW - Cyclic GMP

KW - Cyclic GMP-dependent protein kinase

KW - Non-NMDA glutamate receptors

KW - Oligodendroglia

KW - Protein phosphatases

UR - http://www.scopus.com/inward/record.url?scp=0033979856&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033979856&partnerID=8YFLogxK

U2 - 10.1046/j.1471-4159.2000.740633.x

DO - 10.1046/j.1471-4159.2000.740633.x

M3 - Article

C2 - 10646514

AN - SCOPUS:0033979856

VL - 74

SP - 633

EP - 640

JO - Journal of Neurochemistry

JF - Journal of Neurochemistry

SN - 0022-3042

IS - 2

ER -