A comparison of the effects of penicillamine, trientine, and trithiomolybdate on [35S]-labeled metallothionein in vitro; implications for Wilson's disease therapy.
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| Abstract |
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.
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| Authors | A McQuaid, J Mason |
| Journal | Journal of inorganic biochemistry (J Inorg Biochem) Vol. 41 Issue 2 Pg. 87-92 (Feb 01 1991) ISSN: 0162-0134 [Print] United States |
| PMID | 2033396 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't) |
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