Abstract
Summary
Recent evidence indicates that hypersensitivity reactions, produced in rats by the administration of a protein antigen, alters plasma zinc and iron homeostasis by depressing concentrations of these trace minerals. Studies were performed to determine if altered zinc homeostasis involves, in part, enhanced hepatic metallothionein (MT) synthesis. MT, a high cysteine-containing cytoplasmic protein, possesses a high affinity for zinc and other heavy metals and has been implicated in zinc homeostasis.
Antigen challenge (0.5 mg BSA) in rats previously sensitized with either 5 or 10 mg BSA produced a significant decrease in plasma zinc and iron concentrations within 7 hr in an apparent dose-dependent manner. Plasma zinc depression was accompanied by an increase in hepatic MT content as well as MT-associated total Zn and 65Zn used to pulse-label the metalloprotein. The depression in plasma zinc, but not iron, and the enhanced synthesis of MT was significantly reduced by prior treatment of rats with actinomycin D. This finding suggests a requirement for new mRNA synthesis for zinc, but not iron alterations during hypersensitivity reactions. Results support the concept that induction of hepatic MT may be a common mechanism involved in altered plasma zinc homeostasis regardless of the initiating pathophysiologic condition.
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