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Cyclic GMP/Cyclic GMP‐Dependent Protein Kinase System Prevents Excitotoxicity in an Immortalized Oligodendroglial Cell Line
Author(s) -
Yoshioka Akira,
Yamaya Yoko,
Saiki Shinji,
Kanemoto Masumi,
Hirose Genjiro,
Pleasure David
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.740633.x
Subject(s) - forskolin , ibmx , activator (genetics) , staurosporine , protein kinase a , chemistry , phosphodiesterase , cycloheximide , kainate receptor , cyclic nucleotide , second messenger system , medicine , phosphodiesterase inhibitor , excitotoxicity , endocrinology , kinase , biochemistry , biology , intracellular , glutamate receptor , protein biosynthesis , receptor , nucleotide , gene , enzyme , ampa receptor
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 Ca 2+ 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 Ca 2+ 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 Iβ mRNA, but no translation of PKG Iα mRNA. Therefore, we concluded that the cyclic GMP/PKG system prevents OLC excitotoxicity.