Metallothionein (MT), a low molecular weight, cysteine-rich metal binding p
rotein, has been associated with cytoprotection from heavy metals and cellu
lar oxidants, As MT has the ability to scavenge hydroxyl radicals, MT may c
ontrol intracellular redox status. In the present study, we examined whethe
r MT regulates the activity of nuclear factor-kappa B (NF-kappa B), which i
s one of the redox-regulated transcription factors, using the MT null embry
onic cell lines established from MT null mice. We first found that tumor ne
crosis factor (TNF)-induced activation of the binding of NF-kappa B protein
to DNA in wild type MT+/+ cells was lower than that in MT-/- cells. The NF
-kappa B activation in MT-expressing cells established from MT-/- cells by
the transfection of mouse MT-I gene was also significantly tower than that
in MT-/- cells, In addition, transfection of the MT gene inhibited TNF-indu
ced I kappa B degradation and suppressed NF-kappa B-dependent gene expressi
on induced by TNF, These results demonstrate that MT may function as a nega
tive regulator of NF-kappa B activity. (C) 1999 Federation of European Bioc
hemical Societies.