Author/Editor		Horvat, Anemari; Muhič, Marko; Smolič, Tina; Begić, Ena; Zorec, Robert; Kreft, Marko; Vardjan, Nina
Title		Ca[sup]2+ as the prime trigger of aerobic glycolysis in astrocytes
Type		članek
Publication year		2021
Volume		str. str.
ISSN		0143-4160 - Cell calcium
Language		eng
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 [alpha]1-/[beta]-AR-mediated Ca2+/cAMP signals, [beta]-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 [alpha]1-/[beta]-AR-mediated increases in [glc]i and [lac]i were reduced by %65 % and %30 %, respectively, indicating that at least %30 % of the utilization of d-glucose is linked to glycogen remodelling and aerobic glycolysis. Additional activation of [beta]-AR/cAMP signals aided to [alpha]1-/[beta]-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.
Keywords		astrocytes aerobic glycolysis d-glucose astrociti aerobna glikoliza d-glukoza