Metallothionein and trace element metabolism in sheep tissues in response to high and sustained zinc dosages. 1. Characterization and turnover of metallothionein isoforms

Abstract

Romney wether sheep were given ZnO on a regular basis, as required in protocols for the treatment of facial eczema, at either 12 g ZnO fortnight-1 or 12 g ZnO week-1, and the effect of Zn on the synthesis of different metallothionein (MT) isoforms isolated from liver tissue characterized and quantified. Metallothionein isoforms in liver of dosed and non-dosed sheep were quantitatively determined by reverse phase HPLC, with markedly increased concentrations of total MT-Ia protein found in the liver tissue of Zn-dosed groups (634 pg g-l fresh weight for the weekly dosed group) compared with 49 pg g-1 fresh weight in non-dosed sheep. The concentration of MT-II protein was not significantly increased. Individual sheep varied widely in the relative amounts of each MT isoform expressed with increased amounts of types of MT-Ia especially, and MT-I1 in some animals, which bound predominantly Cu. The half-lives for [35S]-cysteine and 67Zn in MT isoforms from weekly dosed sheep were found to be 2.5-3.5 days and 5-24 h respectively, indicating relatively fast exchange of Zn with MT compared with synthesis. Rate of synthesis for MT-Ia was twice that for MT-11. Data reflecting relationships between MT isoforms, Cu and Zn concentrations in liver are presented and discussed.