Nanomolar nitric oxide concentrations quickly and reversibly modulate astrocytic energy metabolism

Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic e...

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Bibliographic Details
Published in:The Journal of biological chemistry 2017-06, Vol.292 (22), p.9432-9438
Main Authors: San Martín, Alejandro, Arce-Molina, Robinson, Galaz, Alex, Pérez-Guerra, Gustavo, Barros, L. Felipe
Format: Article
Language:English
Subjects:
Animals
AR-C155858
astrocyte
Astrocytes - metabolism
cytochalasin B
cytochrome c oxidase (complex IV)
Editors' Picks
Endothelial Cells - metabolism
Energy Metabolism - physiology
Fluorescence Resonance Energy Transfer
glucose metabolism
Glut1
lactate
Lactic Acid - metabolism
MCT
Mice
nitric oxide
Nitric Oxide - metabolism
pyruvate
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Summary:Nitric oxide (NO) is an intercellular messenger involved in multiple bodily functions. Prolonged NO exposure irreversibly inhibits respiration by covalent modification of mitochondrial cytochrome oxidase, a phenomenon of pathological relevance. However, the speed and potency of NO's metabolic effects at physiological concentrations are incompletely characterized. To this end, we set out to investigate the metabolic effects of NO in cultured astrocytes from mice by taking advantage of the high spatiotemporal resolution afforded by genetically encoded Förster resonance energy transfer (FRET) nanosensors. NO exposure resulted in immediate and reversible intracellular glucose depletion and lactate accumulation. Consistent with cytochrome oxidase involvement, the glycolytic effect was enhanced at a low oxygen level and became irreversible at a high NO concentration or after prolonged exposure. Measurements of both glycolytic rate and mitochondrial pyruvate consumption revealed significant effects even at nanomolar NO concentrations. We conclude that NO can modulate astrocytic energy metabolism in the short term, reversibly, and at concentrations known to be released by endothelial cells under physiological conditions. These findings suggest that NO modulates the size of the astrocytic lactate reservoir involved in neuronal fueling and signaling.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.M117.777243