TPA and cycloheximide modulate the activation of NF‐κB and the induction and stability of nitric oxide synthase transcript in primary neonatal rat hepatocytes
- 5 February 1996
- journal article
- Published by Wiley in FEBS Letters
- Vol. 379 (3) , 279-285
- https://doi.org/10.1016/0014-5793(95)01527-2
Abstract
12-O-Tetradecanoylphorbol 13-acetate (TPA) elicited a transient increase in the transcription of the inducible nitric oxide synthase (iNOS) gene coupled with a shortening of the half-life of its mRNA in primary neonatal rat hepatocytes. These effects of TPA were preceded by a surge in nuclear translocation of the transcription factor NF-κB, and followed by a mounting accumulation of NO2 − in the growth medium. Even cycloheximide (CHX) added by itself elicited an early, sustained activation of NF-κB followed by an intense induction of iNOS gene expression, irrespective of what degree of protein synthesis inhibition was brought about by the several concentrations tested. When given together, TPA and CHX exerted additive effects on hepatocellular iNOS mRNA levels. These results suggest the likelihood of an ordered sequence of events by which an activated NF-κB mediates the induction of iNOS gene expression in TPA- and/or CHX-treated primary hepatocytes.Keywords
This publication has 38 references indexed in Scilit:
- Co-induction of Arginase and Nitric Oxide Synthase in Murine Macrophages Activated by LipopolysaccharideBiochemical and Biophysical Research Communications, 1995
- Pyrrolidine Dithiocarbamate Prevents IL-1-Induced Nitric Oxide Synthase mRNA, but Not Superoxide Dismutase mRNA, in Insulin Producing CellsBiochemical and Biophysical Research Communications, 1995
- NITRIC OXIDE: A Physiologic Messenger MoleculeAnnual Review of Biochemistry, 1994
- Pyrrolidine Dithiocarbamate Differentially Affects Interleukin 1β- and cAMP-Induced Nitric Oxide Synthase Expression in Rat Renal Mesangial CellsBiochemical and Biophysical Research Communications, 1994
- Regulation of hepatocyte albumin and α1-acid glycoprotein secretion by monokines, dexamethasone, and nitric oxide synthase pathway: Significance of activated liver nonparenchymal cellsDigestive Diseases and Sciences, 1994
- Oxidative Stress Induces NFκB DNA Binding and Inducible NOS mRNA in Human Epithelial CellsBiochemical and Biophysical Research Communications, 1994
- Transforming Growth Factor β Differentially Modulates the Inducible Nitric Oxide Synthase Gene in Distinct Cell TypesBiochemical and Biophysical Research Communications, 1993
- Hepatocytes and Macrophages Express an Identical Cytokine-Inducible Nitric Oxide Synthase GeneBiochemical and Biophysical Research Communications, 1993
- The exposure of carcinogen-initiated primary neonatal rat hepatocytes to tumor promoters modulates both the transcripts and the enzymatic activity of nuclear poly(ADP-ribose) polymeraseBiochemical and Biophysical Research Communications, 1992
- A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye bindingAnalytical Biochemistry, 1976