Multiple mechanisms by which glutamine synthetase levels are controlled in murine tissue culture cells.
We report the isolation of a complimentary DNA (cDNA) clone encoding glutamine synthetase, derived from a population of methionine sulfoxime-resistant mouse GF1 fibroblasts. When GF1 cells are incubated for 48 h in the presence of the glucocorticoid hormone dexamethasone, the specific activity of glutamine synthetase (GS), assayed as glutamyltransferase activity, increases by threefold. Based on dot hybridization analysis, hormonal treatment also produces a similar increase in the level of GS mRNA. When GF1 cells or mouse Neuro 2A neuroblastoma cells are transferred from medium containing 4 mM glutamine to glutamine-free medium, glutamyltransferase activity increases by at least fivefold. However, the presence or absence or glutamine in the medium does not affect the relative level of glutamine synthetase mRNA in either cell line. With both GF1 and Neuro 2A cells, the half-time for the decline in glutamine synthetase enzyme activity on addition of glutamine to the medium is approximately 1.5 h. This rapid decline, coupled with the lack of effect of glutamine on the level of GS messenger RNA in Neuro 2A cells, renders it unlikely that neural cells alter glutamine synthetase levels in response to glutamine by a biosynthetic mechanism, as suggested by previous authors [L. Lacoste, K.D. Chaudhary, and J. Lapointe (1982) J. Neurochem. 39, 78-85].
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000032:analysis; D003907:Dexamethasone / Q000494:pharmacology; D005974:Glutamate-Ammonia Ligase / Q000235:genetics / Q000378:metabolism*; D005973:Glutamine / Q000494:pharmacology; D009693:Nucleic Acid Hybridization; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D012333:RNA, Messenger; D005973:Glutamine; D003907:Dexamethasone; D004247:DNA; D005723:gamma-Glutamyltransferase; D005974:Glutamate-Ammonia Ligase