The in vivo effects of maleate on the cation-distribution in rat kidney metallothionein sub-fractions after induction by cadmium and/or mercury.
The metallothionein fractions, isolated by gel filtration from the kidneys of rats that have been dosed with Cd2+, Hg2+ or Cd2+ followed by Hg2+, yield very different elution profiles on ion-exchange chromatography. The metallothionein from Cd2+-treated animals is resolved into the isomethallothioneins I and II and a minor, less negatively-charged species (B), which contains Cd2+ and copper, but little Zn2+. The corresponding fraction from the kidneys of rats doses with Hg2+ yields five components, all of which contain Hg2+, Zn2+ 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 Hg2+-binding component. The distribution of Hg2+ and of other cations between these five sub-fractions, but not the number of sub-fractions, is altered by Cd2+-pretreatment of the animals. Treatment of Cd2+-dosed rats with sodium maleate has no significant effect on the distribution of cations (Cd2+, Zn2+ and copper) amongst the renal metallothionein subfractions. The same treatment, applied to animals dosed with either Hg2+ only, or Cd2+ followed by Hg2+, causes the elimination of 70--75% of the Hg2+ from the metallothionein fraction. Loss occurs from all subfractions, but is greatest in subfraction B, which also loses copper. Whilst it is possible that Hg2+ may induce metallothionein and other metalloproteins in the kidney, Hg2+ appears to bind to both isometallothioneins I and II, when these are induced by Cd2+-pretreatment. The loss of Hg2+, but not of Cd2+, 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.
D000818:Animals; D002104:Cadmium / Q000378:metabolism / Q000494:pharmacology*; D003300:Copper / Q000378:metabolism; D005260:Female; D005650:Fumarates / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism; D008298:Maleates / Q000494:pharmacology*; D008628:Mercury / Q000494:pharmacology*; D008657:Metabolic Clearance Rate; D008667:Metalloproteins / Q000378:metabolism*; D008668:Metallothionein / Q000378:metabolism*; D051381:Rats; D015032:Zinc / Q000378:metabolism
D005650:Fumarates; D008298:Maleates; D008667:Metalloproteins; D002104:Cadmium; D003300:Copper; D008668:Metallothionein; D008628:Mercury; D015032:Zinc