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  • Enhancement of inducible-type NO synthase gene transcription by protein synthesis inhibitors. Activation of an intracellular signal transduction pathway by low concentrations of cycloheximide.

    FEBS Lett. 338(3):326-30. February 7, 1994. View on PubMed.
  • Authors

    Alessandro Weisz (Laboratory of Molecular Medicine and Genomics), Oguchi S, and Esumi H
  • Abstract

    Treatment of mouse macrophage-like RAW 264.7 cells with certain protein synthesis inhibitors is followed by accumulation of the mRNA for the inducible isoform of nitric oxide synthase (i-NOS). The activity of these compounds on the i-NOS gene in RAW 264.7 cells was analyzed here in detail. Results show that both cycloheximide and anisomycin can efficiently induce i-NOS mRNA, even when used at concentrations so low (0.25 microgram/ml) to have only negligible effects on protein synthesis; puromycin, on the other hand, shows only a limited effect on i-NOS mRNA expression, detectable only when cells are treated with higher concentrations of inhibitor (25 micrograms/ml). In RAW 264.7 cells, low concentrations of cycloheximide trigger an immediate-early gene response, as indicated by induction of c-fos and JE mRNAs, and can efficiently activate transcription of transiently transfected recombinant reporter genes including either the i-NOS or the c-fos gene promoters.

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