Ubiquinone protects cultured neurons against spontaneous and excitotoxin-induced degeneration.
Ubiquinone is an endogenous quinone with pharmacological actions mainly related to its antioxidant properties. Here we report that ubiquinone protects cultured cerebellar granule cells against glutamate-induced neurotoxicity. In control cultures at 9 days of maturation in vitro (DIV), a 30-min exposure to 100 microM glutamate induced neuronal degeneration, as reflected by the great percentage (greater than 90%) of cells labeled with propidium iodide 24 h after the exposure. Glutamate-induced neuronal death was dramatically reduced in cultures treated daily with ubiquinone since the second DIV. In these cultures, glutamate failed to induce a "delayed" increase in the influx of 45Ca2+, an established parameter of excitotoxicity. Similarly, repeated addition of ubiquinone attenuated in a concentration-dependent manner the age-dependent degeneration of granule cells that is due to the toxic action of the endogenous glutamate progressively released into the medium. These results suggest that ubiquinone may be a useful drug in the therapy of acute and chronic neurodegenerative diseases related to hyperactivity of excitatory amino acid neurotransmission.
Institute of Pharmacology, University of Catania, Italy.
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Nicoletti
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Scapagnini
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D000818:Animals; D002118:Calcium / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects*; D002478:Cells, Cultured; D002531:Cerebellum / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005971:Glutamates / Q000009:adverse effects; D018698:Glutamic Acid; D009422:Nervous System Diseases / Q000139:chemically induced; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009498:Neurotoxins / Q000009:adverse effects*; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D014451:Ubiquinone / Q000494:pharmacology*
D005971:Glutamates; D009498:Neurotoxins; D016194:Receptors, N-Methyl-D-Aspartate; D014451:Ubiquinone; D018698:Glutamic Acid; D002118:Calcium