Polyhydroxylated C(60), fullerenols, as glutamate receptor antagonists and neuroprotective agents
Autor: | H, Jin, W Q, Chen, X W, Tang, L Y, Chiang, C Y, Yang, J V, Schloss, J Y, Wu |
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Rok vydání: | 2000 |
Předmět: |
Intracellular Fluid
Glutamic Acid Ferric Compounds Rats Sprague-Dawley Fetus Chlorides Receptors GABA Pregnancy Animals Cells Cultured Neurons Binding Sites Cell Death Brain Free Radical Scavengers Hydrogen Peroxide Carbon Rats Receptors Neurotransmitter Neuroprotective Agents Receptors Glutamate Nerve Degeneration Calcium Female Fullerenes Excitatory Amino Acid Antagonists |
Zdroj: | Journal of neuroscience research. 62(4) |
ISSN: | 0360-4012 |
Popis: | Derivatives of C(60) have been shown to be effective free radical scavengers. Hence, many of the biological functions of fullerene are believed to be due to their antioxidant properties. Here we present evidence to show that fullerenols, that are caged fullerene oxides, exert their neuroprotective functions by blocking glutamate receptors and lowering the intracellular calcium, [Ca(2+)](i). In neuronal cultures, fullerenols reduce glutamate-induced neurotoxicity by about 80% at 50microM. No significant effect was observed on H(2)O(2)/Fe(2+)-induced neurotoxicity under the same conditions. Fullerenols were found to inhibit glutamate receptor binding in a dose-dependent manner inhibiting 50% of glutamate binding at 50 microM. Furthermore, AMPA receptors were found to be more sensitive to fullerenols than NMDA and KA receptors. On the other hand, GABA(A) receptors and taurine receptors were not significantly affected by fullerenols at the same concentrations used, suggesting that fullerenols inhibit primarily the glutamate receptors. In addition, fullerenols were also found to lower glutamate (Glu) receptor-induced elevation of [Ca(2+)](i), suggesting that the underlying mechanism of neuronal protective function of fullerenols is likely due to its ability to block the glutamate receptors and to reduce the level of [Ca(2+)](i). |
Databáze: | OpenAIRE |
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