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Skeletal muscle protein loss due to D-penicillamine results from reduced protein synthesis

Lookup NU author(s): Gavin Falkous, Dr David Mantle


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Reports in the literature indicate that (lie trifunctional amino acid D-penicillamine (D-P) induces a variety of muscle abnormalities, although the mechanisms are unknown. We hypothesised that defects may also arise due to the effects of D-P on rates of protein synthesis, possibly via changes in muscle metal composition. Male Wistar rats were injected with D-P at doses of 50 and 500 mg/kg body weight, i.p. Rats designated as controls were injected with 0.15 mol/l NaCl. After 24 h, there were reductions in muscle protein contents, protein synthetic capacities (RNA:protein ratio), fractional rates of protein synthesis, synthesis rates per unit RNA and synthesis rates per unit DNA in skeletal muscles of D-P treated rats. There were no statistically significant differences between the responses of the muscles containing a predominance of either Type I (represented by the soleus) or Type II (represented by the plantaris fibres. In general, intracellular amino acids were not significantly affected by D-P treatment. Changes in muscle metals included significant reductions in copper, iron and manganese, without alterations in zinc or magnesium. In liver D-P reduced copper and iron though zinc, manganese and magnesium were unaffected. These effects of D-P on muscle may have been direct, as plasma indices of liver (activities of alkaline phosphatase and alanine amino transferase) and kidney (urea, creatinine and electrolytes) damage were not significantly altered by D-P treatment. Plasma levels of corticosterone, insulin and free T-3 were also not significantly affected by D-P treatment. Muscle protein carbonyl concentrations, an index of free radical activity, were similarly unaffected. This is the first report of reduced rates of muscle protein synthesis in D-P treatment. Our data suggests that the reduced rates of muscle protein synthesis may contribute to, or reflect, the muscle abnormalities observed in patients undergoing D-P treatment. (C) 2001 Elsevier Science Ltd. Ali rig-hts reserved.

Publication metadata

Author(s): Preedy VR, Wassif WS, Baldwin D, Jones J, Falkous G, Marway JS, Mantle D, Scott DL

Publication type: Article

Publication status: Published

Journal: International Journal of Biochemistry & Cell Biology

Year: 2001

Volume: 33

Issue: 10

Pages: 1013-1026

ISSN (print): 1357-2725

ISSN (electronic): 1878-5875

Publisher: Pergamon


DOI: 10.1016/S1357-2725(01)00062-0


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