Induction by zinc of specific metallothionein isoforms in human monocytes

A low-molecular-mass zinc-containing protein was isolated by gel permeation and anion-exchange chromatography of lysates of human monocytes induced with zinc acetate. Characterization by sodium dodecyl sulphate/polyacrylamide gel electrophoresis and amino acid sequencing identified the two major charge-separable fractions and an occasionally occurring third fraction as metallothionein-1, metallothionein-2 and metallothionein-0, respectively. Metallothionein-1 was shown to consist of a mixture of isoforms, confirmed as metallothionein-1e, metallothionein-1g and metallothionein-1l by comparison with cDNA sequences obtained by screening a human monocyte cDNA library. We can find no previous observation in the literature of metallothionein-1g at both the protein and RNA level in a non-tumour cell, and of metallothionein-0 in a non-fetal cell or tissue. Since isoform-specific polymerase-chain-reaction amplification showed the presence of metallothionein-0 mRNA in zinc-induced but not in untreated monocytes, these cells can be used as an in vitro system to investigate the expression of this previously considered fetal isoform.