Effects of intracellular zinc depletion on metallothionein and ZIP2 transporter expression and apoptosis

Zinc is critical for the functional and structural integrity of cells. We h ave used the monocytic cell line THP-1 as a model in which to study both th e responsiveness of metallothionein and ZIP2 transporter expression to zinc depletion induced by the intracellular zinc chelator TPEN [N,N,N',N'-tetra kis(2-pyridylmethyl) ethylenediamine] and the extent of concomitant apoptos is. Metallothionein expression increased proportionately with the addition of zinc to the medium and decreased with TPEN treatment. When treated with TPEN, both THP-1 cells and human peripheral blood mononuclear cells exhibit ed marked decreases in cellular zinc concentrations and increases in ZIP2 m RNA expression. These results suggest that cells attempt to homeostatically adjust to zinc depletion. When THP-1 cells were treated with >5 muM TPEN, cell viability decreased, and cells entered the early stages of apoptosis. These data show that metallothionein and ZIP2 expression are inversely rela ted during zinc depletion and that apoptosis is concurrent with these chang es.