The in vivo effects of maleate on the cation-distribution in rat kidney metallothionein sub-fractions after induction by cadmium and/or mercury

Abstract

The metallothionein fractions, isolated by gel filtration from the kidneys of rats that have been dosed with Cd 2+, Hg 2+ or Cd 2+ followed by Hg 2+, yield very different elution profiles on ion-exchange chromatography. The metallothionein from Cd 2+-treated animals is resolved into the isomethallothioneins I and II and a minor, less negatively-charged species (B), which contains Cd 2+ and copper, but little Zn 2+. The corresponding fraction from the kidneys of rats dosed with Hg 2+ yields five components, all of which contain Hg 2+, Zn 2+ and Cu, but in different ratios. Three of these compounds correspond in their elution characteristics from DE-cellulose with the above-mentioned isometallothioneins I and II and fraction B. The last of these, which also is rich in Cu, is the major Hg 2+-binding component. The distribution of Hg 2+ and of other cations between these five sub-fractions, but not the number of sub-fractions, is altered by Cd 2+-pretreatment of the animals. Treatment of Cd 2+-dosed rats with sodium maleate has no significant effect on the distribution of cations (Cd 2+, Zn 2+ and copper) amongst the renal metallothionein subfractions. The same treatment, applied to animals dosed with either Hg 2+ only, or Cd 2+ followed by Hg 2+, causes the elimination of 70–75% of the Hg 2+ from the metallothionein fraction. Loss occurs from all subfractions, but is greatest in subfraction B, which also loses copper. Whilst it is possible that Hg 2+ may induce metallothionein and other metalloproteins in the kidney, Hg 2+ appears to bind to both isometallothioneins I and II, when these are induced by Cd 2+-pretreatment. The loss of Hg 2+, but not of Cd 2+, from these metalloproteins after treatment with sodium maleate may be related to differences in the relative binding affinities of the two cations for thionein and other cellular proteins.