title: Physiological amounts of ascorbate potentiate phorbol ester-induced nuclear-binding of AP-1 transcription factor in cells of macrophagic lineage.
abstract: The aim of the reported research was to assess the potential modulatory effect exerted by physiological amounts of ascorbate complexed or not to iron on activator protein 1 (AP-1) nuclear binding. The metal-vitamin complex was shown able to strongly potentiate AP-1 binding as induced by phorbol 12-myristate 13-acetate (PMA). Such enhancing activity by ascorbate was not observed on PMA-dependent induction of another redox-sensitive transcription factor nuclear factor kappaB (NF-kappaB). Experiments performed in the presence of the metal chelator desferrioxamine (DFO) clearly indicated that ascorbate rather than iron was responsible for the potentiation of PMA effect. The composition of AP-1 heterodimers revealed c-Jun, Jun D, and c-Fos as the major subunits upon PMA +/- ascorbate stimulation. The change in AP-1 components consequent to such stimuli was mainly dependent upon new synthesis. In fact, protein synthesis inhibitor cycloheximide (CHX) prevented the stimulation of AP-1 nuclear binding due to PMA and ascorbate plus PMA. Further, the vitamin was able to amplify the PMA-dependent induction of p38 and pJNK. Thus, a fine modulation of critical thiols by the vitamin along the MAPK pathway is conceivable.
authors.affiliation: Department of Clinical and Biological Sciences, University of Torino, S. Luigi Gonzaga Hospital, 10043 Orbassano, Torino, Italy.
authors.forename: M C
authors.initials: MC
authors.lastname: Arkan
authors.forename: G
authors.initials: G
authors.lastname: Leonarduzzi
authors.forename: F
authors.initials: F
authors.lastname: Biasi
authors.forename: H
authors.initials: H
authors.lastname: Başağa
authors.forename: G
authors.initials: G
authors.lastname: Poli
mesh_terms: D000818:Animals; D001205:Ascorbic Acid / Q000494:pharmacology*; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D003676:Deferoxamine / Q000494:pharmacology; D019281:Dimerization; D004357:Drug Synergism; D008264:Macrophages / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D010084:Oxidation-Reduction; D021122:Protein Subunits; D016755:Proto-Oncogene Proteins c-jun / Q000737:chemistry / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D016328:NF-kappa B; D021122:Protein Subunits; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; D003513:Cycloheximide; D020928:Mitogen-Activated Protein Kinases; D003676:Deferoxamine; D013755:Tetradecanoylphorbol Acetate; D001205:Ascorbic Acid