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Role of Copper in the Regulation and Accumulation of Superoxide Dismutase and Metallothionein in Rat Liver¹

Department of Nutrition, University of California, Davis, CA 95616

Weanling male Sprague-Dawley rats were fed one of four diets that varied in Cu, Zn or Cd content. To the control diet (I) Cu, Zn and Cd were added at 10, 100 and 0 mg/kg diet, respectively. Diets II and III also contained 10 mg/kg of dietary Cu, except that Zn was elevated to 1000 mg/kg for diet II, or Cd was added at 10 mg/kg for diet III. Diet IV was deficient in Cu (<1 mg/kg) with Zn at 100 mg/kg and no added Cd. At wk 6 post-weaning, half of the rats fed diets I and IV were injected once with Cd acetate (5 mg Cd/kg body weight). The immediate response to Cd injection was an increase in metallothionein accumulation (three- to fourfold) and in Cu,Zn superoxide dismutase (SOD) accumulation (1.2- to 1.5-fold) in liver. SOD was estimated in an ELISA. These responses were not influenced by a change in Cu status (I vs. IV). However, in functional assays, SOD enzymatic activity was about half that of the control values. In this regard, SOD appears to be given high priority with respect to the utilization of cellular Cu, i.e., a 10-fold reduction in hepatic Cu only resulted in a twofold reduction in SOD activity and the amount of apoenzyme remained at normal levels.

KEY WORDS: • copper • superoxide dismutase • metallothionein

¹ This work was funded in part by National Institutes of Health Grant No. 3-P30-DK-35747, administered by the Clinical Nutrition Research Unit, Division of Clinical Nutrition, University of California, Davis, School of Medicine and by National Institutes of Health Grant No. RO1-HL-15965.

Manuscript received 30 December 1987. Revision accepted 3 March 1988.