Trace elements in regulation of NF-κB activity

Summary ent years several studies have shown that NT-κB might be a very important therapeutic target in the treatment of various chronic inflammatory, degenerative and tumour diseases. Trace elements play essential roles in the regulation of cell signaling mechanisms via transcription factors and a large number of genes. An important aspect of the present review is the description of the mechanisms by which trace elements might influence transcription factor NF-κB. nding activity of NF-κB is regulated by the redox state of the cysteine residue (Cys-62) in the DNA binding domain of the p50 subunit and impaired by different metals (Co, Cr, Ni, Cd, Pb). It has been hypothesised that the broad specificity of interrelationships between NF-κB, AP-1 and various metals results from interactions of metals with specific moieties of transcription factors and IκB-kinases, as well as from the existence of a metalgoverned redox system. The hypothetical targets in the NF-κB signaling pathway affected by metals are: IκB-kinases, IκBs, NF-κB, proteasome degradation of NF-κB, κB-sites in DNA. Possibly, this system is required by the cell for adequate regulation of the transcription machinery in response to changes in intracellular and intranuclear fluxes of metals and radicals and is very ancient evolutionary mechanism of stress adaptation. le of the NF-κB-mediated mechanism in induction or prevention of chronic inflammatory, allergic, degenerative and tumor diseases by zinc, vanadium, manganese, copper, silica, iodine and other trace elements is discussed.