Ca2+ as the prime trigger of aerobic glycolysis in astrocytes.
Cell Calcium
; 95: 102368, 2021 05.
Article
em En
| MEDLINE
| ID: mdl-33621899
ABSTRACT
Astroglial aerobic glycolysis, a process during which d-glucose is converted to l-lactate, a brain fuel and signal, is regulated by the plasmalemmal receptors, including adrenergic receptors (ARs) and purinergic receptors (PRs), modulating intracellular Ca2+ and cAMP signals. However, the extent to which the two signals regulate astroglial aerobic glycolysis is poorly understood. By using agonists to stimulate intracellular α1-/ß-AR-mediated Ca2+/cAMP signals, ß-AR-mediated cAMP and P2R-mediated Ca2+ signals and genetically encoded fluorescence resonance energy transfer-based glucose and lactate nanosensors in combination with real-time microscopy, we show that intracellular Ca2+, but not cAMP, initiates a robust increase in the concentration of intracellular free d-glucose ([glc]i) and l-lactate ([lac]i), both depending on extracellular d-glucose, suggesting Ca2+-triggered glucose uptake and aerobic glycolysis in astrocytes. When the glycogen shunt, a process of glycogen remodelling, was inhibited, the α1-/ß-AR-mediated increases in [glc]i and [lac]i were reduced by â¼65 % and â¼30 %, respectively, indicating that at least â¼30 % of the utilization of d-glucose is linked to glycogen remodelling and aerobic glycolysis. Additional activation of ß-AR/cAMP signals aided to α1-/ß-AR-triggered [lac]i increase, whereas the [glc]i increase was unaltered. Taken together, an increase in intracellular Ca2+ is the prime mechanism of augmented aerobic glycolysis in astrocytes, while cAMP has only a moderate role. The results provide novel information on the signals regulating brain metabolism and open new avenues to explore whether astroglial Ca2+ signals are dysregulated and contribute to neuropathologies with impaired brain metabolism.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Astrócitos
/
Cálcio
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Glucose
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Glicólise
Limite:
Animals
Idioma:
En
Revista:
Cell Calcium
Ano de publicação:
2021
Tipo de documento:
Article
País de afiliação:
Eslovênia