Effects of pyrroloquinoline quinone on glutamate-induced production of reactive oxygen species in neurons

• Published in: European journal of pharmacology Vol. 326; no. 1; pp. 67 - 74
• Main Authors: Scanlon, Joelle M, Aizenman, Elias, Reynolds, Ian J
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 12-05-1997; Elsevier
• Subjects: Animals; Biological and medical sciences; Cells, Cultured; Dihydroethidium; Excitatory Amino Acid Antagonists - pharmacology; Free radical; Free Radical Scavengers - pharmacology; Glutamate; Glutamic Acid - pharmacology; Hydrogen Peroxide - metabolism; Medical sciences; Microscopy, Fluorescence; Neurons - drug effects; Neurons - metabolism; Neuropharmacology; Neuroprotective agent; Neuroprotective Agents - pharmacology; NMDA receptor; Oxidants - metabolism; Oxidation-Reduction; Pharmacology. Drug treatments; PQQ Cofactor; Pyrroloquinoline quinone; Quinolones - pharmacology; Rats; Rats, Sprague-Dawley; Reactive Oxygen Species - metabolism; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - drug effects; Redox modulatory site; Dihydroethidium; Redox modulatory site; Pyrroloquinoline quinone; Glutamate; NMDA receptor; Free radical; Embryo; Oxygen; Rat; Rodentia; Central nervous system; Neuroprotective agent; Glutamate receptor; Frontal cortex; In vitro; Radical scavenger; Vertebrata; Regulation(control); Mammalia; Animal; Excitatory aminoacid; Primary culture; Redox system; Mechanism of action; Brain (vertebrata)
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/S0014-2999(97)00137-4

Pyrroloquinoline quinone may act as a free radical scavenger and also as a modulator of the NMDA receptor associated redox modulatory site. Using the oxidation sensitive dye dihydroethidium, we examined the effects of pyrroloquinoline quinone on free radical production in cultured forebrain neurons following glutamate receptor activation. Both glutamate (100 μM) and hydrogen peroxide (30 mM) produced a rapid increase in dihydroethidium fluorescence indicating dye oxidation. Pyrroloquinoline quinone (5–200 μM) effectively inhibited dihydroethidium fluorescence induced by glutamate but not by hydrogen peroxide. Glutamate-induced dihydroethidium fluorescence was inhibited by the thiol oxidant 5,5′-dithio-bis(2-nitrobenzoic acid) (DTNB). Pyrroloquinoline quinone (50 μM) inhibited glutamate responses in control and in dithiothreitol treated neurons. However, pyrroloquinoline quinone did not further decrease the response to glutamate in DTNB treated neurons. These results suggest that pyrroloquinoline quinone inhibits the free radical-generating response to glutamate by oxidizing the NMDA receptor redox site and not by scavenging reactive oxygen species.