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Inhibitory effects of heavy metals on transcription factor Sp1
1Division of Hazard Assessment, National Institute of Industrial Health, Kawasaki, Japan.
Abstract:
Heavy metals are expected to affect the biological activity of various metal-containing proteins, including transcriptional regulators. We studied the effects of several heavy metal ions on the DNA-binding activity of a Zn-finger transcription factor, Sp1. With respect to both DNA elements through which Sp1 acts positively and negatively, Cd2+ inhibited DNA-binding of Sp1 at 20 microM or higher, while the toxic effect of Zn2+ was obvious only at more than 200 microM. Inhibition was also apparent for Cu2+ but less remarkable for Hg2+. The inhibition by Cd2+ was relieved by the addition of Zn2+ at much lower concentrations than that of Cd2+. These results suggest that the toxic potential of heavy metals could be largely influenced by the intracellular Zn2+ concentration.