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 language | English (US) |
|---|---|
| Pages (from-to) | 633-640 |
| Number of pages | 8 |
| Journal | Journal of Neurochemistry |
| Volume | 74 |
| Issue number | 2 |
| DOIs | |
| State | Published - 2000 |
| Externally published | Yes |
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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 journal › Article
}
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 -