title: Up-regulation of glutamine synthesis in microglia activated with endotoxin.
abstract: We previously verified that newborn rat brain-derived microglia have the ability to uptake (14)C-glutamate (Glu) through glutamate transporter-1. A given amount of Glu incorporated into microglia was suspected to be metabolized to glutamine (Gln). However, the ability of microglia to do this had not been demonstrated. Thus, in the present study we examined the possibility that primary rat microglia metabolize Glu into Gln. Immunocytochemical and immunoblotting studies indicated that the microglia express glutamine synthetase (GS) protein. As expected from these results, GS activity was actually detected in microglia, although the specific activity was lower than that of astrocytes. Considering this microglial property, it seemed possible that the taken Glu is metabolized to Gln in the cells. To investigate this possibility, we exposed microglia to [(13)C]Glu-containing medium and analyzed the change of Glu to Gln in a nuclear magnetic resonance examination. The results clarified that non-stimulated microglia hardly changed Glu to Gln, but when stimulated with lipopolysaccharide the microglia significantly metabolized [(13)C]Glu to [(13)C]Gln. Microglia were thus, strongly suggested to metabolize Glu to Gln via GS activity when activated in the inflammatory/pathological state of the nervous system.
authors: Department of Bioinformatics, Faculty of Engineering, Soka University, Tokyo 192-8577, Japan. Electronic address: nakajima@t.soka.ac.jp.
authors: Kazuyuki
authors: K
authors: Nakajima
authors: Department of Environmental Engineering for Symbiosis, Faculty of Engineering, Soka University, Tokyo 192-8577, Japan.
authors: Tomoyuki
authors: T
authors: Kanamatsu
authors: Department of Bioinformatics, Faculty of Engineering, Soka University, Tokyo 192-8577, Japan.
authors: Yosuke
authors: Y
authors: Takezawa
authors: Department of Neurochemistry, National Institute of Neuroscience, Tokyo 187-8502, Japan.
authors: Shinichi
authors: S
authors: Kohsaka
mesh_terms: D000818:Animals; D005974:Glutamate-Ammonia Ligase / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar
chemical_list: D008070:Lipopolysaccharides; D005973:Glutamine; D018698:Glutamic Acid; D005974:Glutamate-Ammonia Ligase
keywords: Glutamic acid; Glutamine synthetase; Microglia; Nuclear magnetic resonance