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TPA and cycloheximide modulate the activation of NF‐κB and the induction and stability of nitric oxide synthase transcript in primary neonatal rat hepatocytes
Author(s) -
Menegazzi Marta,
Guerriero Chiara,
Carcereri de Prati Alessandra,
Cardinale Caterina,
Suzuki Hisanori,
Armato Ubaldo
Publication year - 1996
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(95)01527-2
Subject(s) - cycloheximide , nitric oxide synthase , nitric oxide , microbiology and biotechnology , messenger rna , transcription (linguistics) , gene expression , transcription factor , biology , protein biosynthesis , hepatocyte , chemistry , biochemistry , gene , endocrinology , in vitro , linguistics , philosophy
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 NO 2 − 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.