Abstract
The second messenger 2′3′-cyclic-GMP-AMP (cGAMP) is thought to be transmitted from brain carcinomas to astrocytes via gap junctions, which functions to promote metastasis in the brain parenchyma. In the current study, we established a method to introduce cGAMP into astrocytes, which simulates the state of astrocytes that have been invaded by cGAMP around tumors. Astrocytes incorporating cGAMP were analyzed by metabolomics, which demonstrated that cGAMP increased glutamate production and astrocyte secretion. The same trend was observed for γ-aminobutyric acid (GABA). Conversely, glutamine production and secretion were decreased by cGAMP treatment. Due to the fundamental role of astrocytes in regulation of the glutamine–glutamate cycle, such metabolic changes may represent a potential mechanism and therapeutic target for alteration of the central nervous system (CNS) environment and the malignant transformation of brain carcinomas.
Highlights
Astrocytes express a variety of transporters and are responsible for central nervous system (CNS) homeostasis and neuronal protection by taking up or releasing numerous substances [1]
The results showed that the amount of cGAMP was below the detection limit in the astrocytes that took up nanoparticles without cGAMP, but that cGAMP was detected in the astrocytes that took up ss-cleavable pH-activated lipid-like material (ssPalm)-cGAMP
Given that the amounts of intracellular Glu and Gln were altered by cGAMP, we examined the mRNA expression of glutamine synthetase (GS), an enzyme that produces
Summary
Astrocytes express a variety of transporters and are responsible for central nervous system (CNS) homeostasis and neuronal protection by taking up or releasing numerous substances [1]. Glucose in the blood is taken up by astrocytes mainly through glucose transporter 1 (GLUT1), which is expressed in endothelial cell walls of capillary vessels and astrocyte membranes. It has been proposed that astrocytes metabolize and release glucose to lactate, which is taken up by neurons and serves as a substrate for the tricarboxylic acid (TCA) cycle (astrocyte–neuron lactate shuttle (ANLS)) [2,3]. Astrocytes are the only cells in the brain that accumulate abundant glycogen granules and can produce lactic acid through the breakdown of glycogen [4]. Astrocytes collect glutamate (Glu) released from presynapses to improve the efficiency of synaptic transmission and prevent neurotoxicity due to excess extracellular
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
