Transcriptional regulation of the rat glutamine synthetase gene by tumor necrosis factor-alpha

    Authors

    R. Chakrabarti

    Comments

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    Abbreviated Journal Title

    Eur. J. Biochem.

    Keywords

    glutamine synthetase; transcription; tumor-necrosis factor; SENSITIVE METHOD; CELLS; PROTEINS; PHOSPHORYLATION; EXPRESSION; CYTOKINES; ENHANCER; BINDING; ENZYME; ASSAY; Biochemistry & Molecular Biology

    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 alpha (TNF-alpha). This paper reports the regulation of GS expression in rat skeletal muscle which expresses high levels of GS. TNF-alpha 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-alpha treatment. To monitor transcriptional activation of GS by TNF-alpha, and to identify a TNF-alpha-responsive element in the GS promoter, L6 cells were treated with TNF-alpha 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-alpha-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-alpha and identifies a TNF-alpha-responsive region at the 5' flanking sequence of the GS gene.

    Journal Title

    European Journal of Biochemistry

    Volume

    254

    Issue/Number

    1

    Publication Date

    1-1-1998

    Document Type

    Article

    Language

    English

    First Page

    70

    Last Page

    74

    WOS Identifier

    WOS:000073841100011

    ISSN

    0014-2956

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