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Supplemental Dietary Cystine Elevates Kidney Metallothionein in Rats by a Mechanism Involving Altered Zinc Metabolism¹

Department of Applied Biochemistry, Faculty of Applied Biological Science, Hiroshima University, Higashi-Hiroshima 724, Japan

Dietary sulfur-containing amino acids influence zinc and copper status. This study was conducted to investigate the relationship between the status of these elements and tissue metailothionein in rats fed diets supplemented with sulfur-containing amino acids. In a series of experiments, a diet containing 100 g casein/kg diet was unsupplemented or supplemented with L-cystine (3–50 g/kg diet) or L-methionine (3 or 30 g/kg diet). Kidney concentrations of zinc and copper in rats fed the diet supplemented with high levels of cystine (25 or 50 g/kg) were significantly higher than those in rats fed the unsupplemented diet. Kidney concentrations of metallothionein and metallothionein mRNA were also significantly higher in rats fed cystine-supplemented diets. There was a correlation (r = 0.838, P < 0.01) between the levels of zinc and metallothionein in kidney of rats fed the diets with different levels of cystine and zinc. However, in the rats fed the diets with different levels of cystine and copper, the correlation was not as strong (r = 0.587, P < 0.01). The changes in kidney metallothionein concentration due to the addition of 3 or 30 g/kg cystine were associated with parallel changes in serum zinc concentration and in apparent absorption of zinc, but not in serum copper concentration or apparent absorption of copper. Addition of 3 or 30 g methionine/kg diet to the diet did not affect kidney concentrations of metallothionein or zinc. These results indicate that supplementation of cystine to the diet can induce kidney metallothionein through a mechanism involving altered zinc metabolism.

KEY WORDS: • metallothionein • zinc • rats • cystine • copper

¹ The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 USC section 1734 solely to indicate this fact.

² To whom correspondence and reprint requests should be addressed.

Manuscript received 8 July 1994. Revision accepted 20 October 1994.