title: Identification of NF-kappaB in the marine fish Stenotomus chrysops and examination of its activation by aryl hydrocarbon receptor agonists.
abstract: Members of the Rel family of proteins have been identified in Drosophila, an echinoderm, Xenopus, birds and mammals. Dimers of Rel proteins form the transcription factor nuclear factor kappaB (NF-kappaB) that rapidly activates genes encoding cytokines, cell surface receptors, cell adhesion molecules and acute phase proteins. Evidence suggests that xenobiotic compounds also may alter the activation of NF-kappaB. This study had a dual objective of identifying members of the Rel family and examining their activation by xenobiotic compounds in a marine fish model, scup (Stenotomus chrysops). A DNA-protein crosslinking technique demonstrated that liver, kidney and heart each had at least three nuclear proteins that showed specific binding to an NF-kappaB consensus sequence, with molecular weights suggesting that the proteins potentially corresponded to mouse p50, p65 (RelA) and c-rel. In addition, an approximately 35kD NF-kappaB binding protein was evident in liver and kidney. The 50 kD protein was immunoprecipitated by mammalian p50-specific antibodies. The presence of Rel members in fish implied by those results was confirmed by RT-PCR cloning of a Rel homology domain (an apparent c-rel) from scup liver. NF-kappaB activation occurred in vehicle-treated fish, but this appeared to decrease over time. In fish treated with 0.01 or 1 mg 3,3',4,4', 5-pentachlorobiphenyl per kg, NF-kappaB activation in liver did not decrease, and there was a 6-8-fold increase in activation 16-18 days following treatment. Treatment with 10 mg benzo[a]pyrene/kg had no effect on NF-kappaB-DNA binding, either at 3 or 6 days following treatment. The data show that the Rel family of proteins is present in fish, represented at least by a p50/105 homologue, and support a hypothesis that some aryl hydrocarbon receptor agonists can activate NF-kappaB in vivo.
authors.affiliation: Biology Department, Redfield 342, MS 32, Woods Hole Oceanographic Institution, Woods Hole, MA 02543, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Schlezinger
authors.forename: C E
authors.initials: CE
authors.lastname: Blickarz
authors.forename: K K
authors.initials: KK
authors.lastname: Mann
authors.forename: S
authors.initials: S
authors.lastname: Doerre
authors.forename: J J
authors.initials: JJ
authors.lastname: Stegeman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002645:Chickens; D016384:Consensus Sequence; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics; D005399:Fishes; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D051379:Mice; D008862:Microsomes, Liver / Q000201:enzymology*; D008969:Molecular Sequence Data; D016328:NF-kappa B / Q000378:metabolism*; D010802:Phylogeny; D011078:Polychlorinated Biphenyls / Q000494:pharmacology*; D020569:Proto-Oncogene Proteins c-rel / Q000235:genetics* / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D014422:Turkeys; D015262:Xenobiotics / Q000494:pharmacology; D014982:Xenopus laevis
chemical_list: D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D018336:Receptors, Aryl Hydrocarbon; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D011078:Polychlorinated Biphenyls