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Oxygen free radicals regulate NMDA receptor function via a redox modulatory site
E Aizenman1, K A Hartnett, I J Reynolds
1Department of Physiology, University of Pittsburgh School of Medicine, Pennsylvania 15261.
Neuron
|December 1, 1990
Summary
Reactive oxygen species oxidize the N-methyl-D-aspartate (NMDA) receptor
Area of Science:
- Neuroscience
- Cellular and Molecular Biology
- Biochemistry
Background:
- A novel redox modulatory site on the N-methyl-D-aspartate (NMDA) receptor has been identified.
- This site is sensitive to sulfhydryl redox reagents.
Purpose of the Study:
- To investigate if this redox modulatory site is susceptible to oxidation by endogenous reactive oxygen species (ROS).
- To determine the functional consequences of ROS-induced oxidation on NMDA receptor activity and neurotoxicity.
Main Methods:
- Utilized cultured cortical neurons.
- Generated oxygen free radicals using xanthine and xanthine oxidase.
- Measured NMDA-induced changes in intracellular free Ca2+ concentrations.
- Recorded NMDA-evoked cation currents.
- Assessed NMDA-mediated neurotoxicity in vitro.
Main Results:
- Oxygen free radicals decreased NMDA-induced Ca2+ influx and cation currents in cortical neurons.
- Free radical production reversed dithiothreitol-enhanced NMDA-mediated neurotoxicity.
- Demonstrated that NMDA receptor function is modulated by endogenous ROS.
Conclusions:
- NMDA receptor function is modulated by its redox site through oxidation by endogenous reactive oxygen species.
- This mechanism is relevant to tissue reperfusion following ischemic events.
- This novel regulatory pathway has implications for understanding glutamate neurotoxicity in vivo.