Inhibitory effects of heavy metals on transcription factor Sp1.
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.
Gong
P
P
Division of Hazard Assessment, National Institute of Industrial Health, Kawasaki, Japan.
Ogra
Y
Y
Koizumi
S
S
D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D019216:Metals, Heavy / Q000009:adverse effects*; D016329:Sp1 Transcription Factor / Q000187:drug effects*; D015032:Zinc / Q000009:adverse effects* / Q000378:metabolism
D019216:Metals, Heavy; D016329:Sp1 Transcription Factor; D015032:Zinc