A comparison of the effects of penicillamine, trientine, and trithiomolybdate on ( sup 35 S)-labeled metallothionein in vitro; implications for Wilson's disease therapy

Journal Article · Fri Feb 01 04:00:00 EST 1991 · Journal of Inorganic Biochemistry; (USA)

DOI:https://doi.org/10.1016/0162-0134(91)80002-Y· OSTI ID:5602909

McQuaid, A; Mason, J ^[1]

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1. Univ. of Dublin (Ireland)

The synthesis of radiolabeled metallothionein was induced in rats in vivo by the injection of CuSO{sub 4} and ({sup 35}S)-cysteine. Treatment of 'cold' rat liver cytosol 'spiked' with purified ({sup 35}S) 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 ({sup 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 ({sup 35}S) 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.

• OSTI ID: 5602909
• Journal Information: Journal of Inorganic Biochemistry; (USA), Journal Name: Journal of Inorganic Biochemistry; (USA) Vol. 41:2; ISSN JIBID; ISSN 0162-0134
• Country of Publication: United States
• Language: English

Related Subjects

550901* -- Pathology-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AMINO ACIDS
ANIMALS
BETA DECAY RADIOISOTOPES
BETA-MINUS DECAY RADIOISOTOPES
BIOLOGICAL EFFECTS
BODY
CARBOXYLIC ACIDS
CHELATING AGENTS
CHEMOTHERAPY
COMPARATIVE EVALUATIONS
COPPER
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DISEASES
DRUGS
ELEMENTS
EVEN-ODD NUCLEI
GLANDS
IN VITRO
ISOTOPE APPLICATIONS
ISOTOPES
LIGHT NUCLEI
LIVER
MAMMALS
METABOLIC DISEASES
METALLOPROTEINS
METALLOTHIONEIN
METALS
NERVOUS SYSTEM DISEASES
NUCLEI
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC SULFUR COMPOUNDS
ORGANS
PENICILLAMINE
PROTEINS
RADIOISOTOPES
RADIOPROTECTIVE SUBSTANCES
RATS
RODENTS
SULFUR 35
SULFUR ISOTOPES
THERAPY
THIOLS
TRACER TECHNIQUES
TRANSITION ELEMENTS
VERTEBRATES