It has been reported that cGAMP (Cyclic 2'3'-GMP-AMP) was transmitted to astrocytes from metastatic brain tumor as a favorable signal for cancers. cGAMP is a selective ligand of STING that introduces an innate immune response, although the role for astrocyte is not yet well understood. We previously succeeded to introduce this hydrophilic compound to astrocyte with lipid nanoparticles (SS-cleavable and pH-Activated-like Material: ssPalm) as a carrier, and it affected astrocytic metabolome. In this study, we aimed to grasp the metabolome shift in detail, especially focused on glutamine (Gln)-glutamate (Glu) axis in astrocyte because of its physiological impact.
The ssPalm-cGAMP complex (cGAMP) or only ssPalm complex (empty) was added to the primary cultured astrocytes. After 6 h, ¹³C5,¹⁵N-Glu uptake was examined to detect new Glu or Gln production. Time-dependent Glu production in cells were significantly increased by cGAMP, whereas Gln production was rather smaller. Regarding metabolic enzymes which involve Gln-Glu axis, GAD1, which promotes Glu catabolism to GABA, was significantly decreased. The trend observed here is different from physiological astrocytes that usually uptake Glu and produce Gln in cells. Further study is needed to clarify the role of this metabolic change in the tumor.