Transcriptional regulation of the rat glutamine synthetase gene by tumor necrosis factor‐α

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Abstract
The expression of glutamine synthetase (GS) is induced in rat skeletal muscle cells (L‐6) in response to treatment with the inflammatory cytokine tumor necrosis factor α (TNF‐α). This paper reports the regulation of GS expression in rat skeletal muscle which expresses high levels of GS. TNF‐α treatment leads to a 3−4‐fold increase in GS activity in a dose‐dependent and time‐dependent manner. Northern‐blot analysis of GS mRNA revealed an increased mRNA concentration, reaching a peak at 12 h in response to TNF‐α treatment. To monitor transcriptional activation of GS by TNF‐α, and to identify a TNF‐α‐responsive element in the GS promoter, L6 cells were treated with TNF‐α following transfection of GS−chloramphenicol‐acetyltransferase (CAT) constructs. The first 251‐bp fragment at the GS upstream sequence showed basal promoter activity, but failed to show any TNF‐α‐inducible activity. However, a 2.5−3‐fold induction was noted in constructs extending up to 1.1 kb. This data demonstrates that the rat GS gene is transcriptionally regulated by TNF‐α and identifies a TNF‐α‐responsive region at the 5′ flanking sequence of the GS gene.

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