Portal de Periódicos da CAPES

A comparison of the effects of Penicillamine, Trientine, and trithiomolybdate on [35S]-labeled metallothionein in vitro; implications for Wilson's disease therapy

1991; Elsevier BV; Volume: 41; Issue: 2 Linguagem: Inglês

10.1016/0162-0134(91)80002-y

1873-3344

Albert McQuaid, James Mason,

Iron Metabolism and Disorders

The synthesis of radiolabeled metallothionein was induced in rats in vivo by the injection of CuSO4 and [35S]-cysteine. Treatment of “cold” rat liver cytosol “spiked” with purified [35S] metallothionein with Penicillamine and Trientine showed that even at relatively high concentrations (up to 50 mg/g liver, wet weight), these compounds had no effect on the copper peak or the position of the [35S] label in the cytosol eluate after Sephadex G-75 gel filtration. By contrast, incubation of the “spiked” liver cytosol with Trithiomolybdate, even at relatively low concentrations (0.5 mg/g liver, wet weight), resulted in a transfer of metallothionein copper to high molecular weight protein fractions; the position of the [35S] apoprotein was unaffected. This copper “stripping” effect on metallothionein supports clinical and other evidence that thiomolybdates have a genuine decoppering effect in vivo whereas Penicillamine and Trientine have another mode of action and indicates that thiomolybdates might provide a more rational alternate therapy for Wilson's disease patients.