Trace elements in regulation of NF-kappaB activity.

In recent years several studies have shown that NF-kappaB might be a very important therapeutic target in the treatment ot various chronic inflammatory, degenerative and tumour diseases. Trace elements play essential roles in the regulation ot cell signaling mechanisms via transcription tactors and a large number of genes. An important aspect of the present review is the description ot the mechanisms by which trace elements might influence transcription factor NF-kappaB. DNA-binding activity of NF-kappaB is regulated by the redox state of the cysteine residue (Gys-62) in the DNA binding domain of the p50 subunit and impaired by different metals (Go, Cr, Ni, Cd, Pb). It has been hypothesised that the broad speciticity of interrelationships between NF-kappaB. AP-1 and various metals results from interactions of metals with specific moieties of transcription factors and IkappaB-kinases, as well as trom the existence of a metal-governed redox system. The hypothetical targets in the NF-kappaB signaling pathway affected by metals are: IkappaB-kinases, IkappaBs, NF-kappaB, proteasome degradation of NF-kappaB, kappaB-sites in DNA. Possibly, this system is required by the cell for adequate regulation ot 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. The role of the NF-kappaB-mediated mechanism in induction or prevention of chronic intlammatory, allergic, degenerative and tumor diseases by zinc, vanadium, manganese, copper, silica, iodine and other trace elements is discussed.