EFFECTS OF PYRROLOQUINOLINE QUINONE ON GLUTAMATE-INDUCED PRODUCTION OF REACTIVE OXYGEN SPECIES IN NEURONS

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 eff ects of pyrroloquinoline quinone on free radical production in culture d forebrain neurons following glutamate receptor activation. Both glut amate (100 mu M) and hydrogen peroxide (30 mM) produced a rapid increa se in dihydroethidium fluorescence indicating dye oxidation. Pyrroloqu inoline quinone (5-200 mu M) effectively inhibited dihydroethidium flu orescence induced by glutamate but not by hydrogen peroxide. Glutamate -induced dihydroethidium fluorescence was inhibited by the thiol oxida nt 5,5'-dithio-bis(2-nitrobenzoic acid) (DTNB). Pyrroloquinoline quino ne (50 mu M) inhibited glutamate responses in control and in dithiothr eitol treated neurons. However, pyrroloquinoline quinone did not furth er decrease the response to glutamate in DTNB treated neurons. These r esults 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.