Metallothionein expression is increased in monocytes and erythrocytes of young men during zinc supplementation

Abstract

The metallothionein gene is transcriptionally regulated by zinc. Consequently, metallothionein has potential for serving as an index of dietary zinc status in humans. To examine this possibility, an enzyme-linked immunoassay (ELISA) based on a sandwich approach that utilizes monoclonal and chicken egg yolk antibodies was used to compare the response of erythrocyte metallothionein protein levels with the response of monocyte metallothionein mRNA levels as measured by competitive reverse transcriptase-polymerase chain reaction (CRT-PCR) during zinc supplementation. Young male subjects participated in an 18-d supplementation study in which zinc was provided at 50 mg/d. Control subjects received a placebo. The zinc supplement resulted tn significantly greater erythrocyte metallothionein levels by d 8 of supplementation compared with controls. Monocyte metallothionein mRNA levels were significantly greater than those of controls by d 2 of supplementation. Both remained elevated through d 18. They returned to base line by 8 and 4 d after supplementation, respectively. The plasma zinc concentration was significantly greater than in controls by d 6 and had returned to control levels by d 22 of supplementation. The results presented here show that both monocyte metallothionein mRNA and erythrocyte metallothionein protein concentrations change in human subjects in response to elevated dietary zinc intake and that monocyte metallothionein mRNA responds more rapidly to elevation of dietary zinc status than erythrocyte metallothionein protein. Consequently, both erythrocyte metallothionein and monocyte metallothionein mRNA may prove to be measures useful for assessment of either zinc depletion or the bioavailability of zinc supplements.