Effects on Metabolism in Astrocytes Caused by cGAMP, Which Imitates the Initial Stage of Brain Metastasis

Autor: Hiroki Tanaka, Hiromi Sato, Masataka Kogane, Hiroto Hatakeyama, Hidetaka Akita, Akihiro Hisaka, Toya Okawa, Momoko Goto, Kurumi Hara, Moe Kikuchi, Daiki Shirane
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: International Journal of Molecular Sciences
Volume 22
Issue 16
International Journal of Molecular Sciences, Vol 22, Iss 9028, p 9028 (2021)
ISSN: 1422-0067
DOI: 10.3390/ijms22169028
Popis: 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.
Databáze: OpenAIRE