20.500.12556/RUL-138438 Ca$^{2+}$ as the prime trigger of aerobic glycolysis in astrocytes 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 Ca$^{2+}$ and cAMP signals. However, the extent to which the two signals regulate astroglial aerobic glycolysis is poorly understood. By using agonists to stimulate intracellular α$_1$-/β-AR-mediated Ca$^{2+}$/cAMP signals, β-AR-mediated cAMP and P$_2$R-mediated Ca$^{2+}$ signals and genetically encoded fluorescence resonance energy transfer-based glucose and lactate nanosensors in combination with real-time microscopy, we show that intracellular Ca$^{2+}$, 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 Ca$^{2+}$-triggered glucose uptake and aerobic glycolysis in astrocytes. When the glycogen shunt, a process of glycogen remodelling, was inhibited, the α$_1$-/β-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 β-AR/cAMP signals aided to α$_1$-/β-AR-triggered [lac]$_i$ increase, whereas the [glc]$_i$ increase was unaltered. Taken together, an increase in intracellular Ca$^{2+}$ 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 Ca$^{2+}$ signals are dysregulated and contribute to neuropathologies with impaired brain metabolism. astrocytes aerobic glycolysis D-glucose L-lactate Ca$^{2+}$/cAMP signalling astrociti aerobna glikoliza d-glukoza true false true Angleški jezik Slovenski jezik Članek v reviji 2022-07-20 14:24:27 2022-07-20 14:24:31 2022-09-15 04:16:45 0000-00-00 00:00:00 2021 0 0 11 str. Vol. 95, art. 102368 May 2021 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 616-092 1532-1991 10.1016/j.ceca.2021.102368 52558339 1-s2.0-S0143416021000221-main.pdf 1-s2.0-S0143416021000221-main.pdf 1 F60C5D8922C802BB3CE3F983BEA3961A fa335dffd4a6172233852d8a87d3caf064501898584bbf0221a9fccc95528894 ec443721-0826-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=158765 https://www.sciencedirect.com/science/article/pii/S0143416021000221 1 a9027532-0826-11ed-8aca-00155dcfd717 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=158764 Medicinska fakulteta Biotehniška fakulteta 0 0 0