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IDENTIFICATION OF NF-KAPPAB IN THE MARINE FISH STENOTOMUS CHRYSOPS AND EXAMINATION OF ITS ACTIVATION BY ARYL HYDROCARBON RECEPTOR AGONISTS. (R827102)
Citation:
Schlezinger, J. J., C. E. Blickharz, K. K. Mann, S. Doerre, AND J. J. Stegeman. IDENTIFICATION OF NF-KAPPAB IN THE MARINE FISH STENOTOMUS CHRYSOPS AND EXAMINATION OF ITS ACTIVATION BY ARYL HYDROCARBON RECEPTOR AGONISTS. (R827102). CHEMICO-BIOLOGICAL INTERACTIONS. Elsevier Science Ltd, New York, NY, 126(2):137-157, (2000).
Description:
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 
B (NF-B) 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-B. 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-B consensus sequence, with molecular weights suggesting that the proteins potentially corresponded to mouse p50, p65 (RelA) and c-rel. In addition, an 
35kD NF-B 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-B 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-B 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-B-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-B in vivo.
Abbreviations: AhR, aryl hydrocarbon receptor; BP, benzo[a]pyrene; CYP, cytochrome P450; EMSA, electrophoretic mobility shift assay; DRE, dioxin response element; IP, immunoprecipitation; NF-B, nuclear factor-B; PeCB, 3,3',4,4',5-pentachlorobiphenyl; ROS, reactive oxygen species