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 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.
From the Centro de Estudios Científicos (CECs), 5110466 Valdivia and aalejo@cecs.cl.|the Universidad Austral de Chile, 5110566 Valdivia, Chile.
Alejandro
A
San Martín
From the Centro de Estudios Científicos (CECs), 5110466 Valdivia and.|the Universidad Austral de Chile, 5110566 Valdivia, Chile.
Robinson
R
Arce-Molina
From the Centro de Estudios Científicos (CECs), 5110466 Valdivia and.
Alex
A
Galaz
From the Centro de Estudios Científicos (CECs), 5110466 Valdivia and.|the Universidad Austral de Chile, 5110566 Valdivia, Chile.
Gustavo
G
Pérez-Guerra
From the Centro de Estudios Científicos (CECs), 5110466 Valdivia and fbarros@cecs.cl.
L Felipe
LF
Barros
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D031541:Fluorescence Resonance Energy Transfer; D019344:Lactic Acid / Q000378:metabolism*; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism*
D009569:Nitric Oxide; D019344:Lactic Acid
AR-C155858; Glut1; MCT; astrocyte; cytochalasin B; cytochrome c oxidase (complex IV); glucose metabolism; lactate; nitric oxide; pyruvate