Metal- and tissue-dependent relationship between metallothionein mRNA and protein.

Metallothionein (MT) expression is transcriptionally regulated but recent evidence suggests that translation of MT mRNA may be regulated under some circumstances (Vasconcelos et al., Biochem. J., 315, 665-671, 1996). A systematic investigation of MT mRNA, protein, and metal levels in liver and kidney of cadmium- or copper-treated rats was made to further understand the relationship between mRNA and protein in particular. Adult rats were injected once with either Cd (8.9 micromol/kg) or Cu(2+) (8.7 micromol/kg) as the chloride salts, and the liver and kidney concentrations of MT-1 and MT-2 mRNA, total soluble MT protein, and tissue Cd, Cu, and Zn were monitored over 48-72 h. The metal composition in the soluble MT protein fraction was also analyzed by on-line size-exclusion chromatography-ICP/MS. Discrepancies between mRNA and protein levels were found in both tissues, but particularly in kidney. Cd treatment significantly increased renal MT-1 and MT-2 mRNA levels but protein was unaffected. In contrast, Cu actually decreased renal MT-1 and MT-2 mRNA but significantly increased MT protein. Cd induced considerably more MT-1 than MT-2 mRNA in liver, but induction of both isoforms was similar in kidney and in liver of Cu-treated rats. Changes in tissue metal levels tended to reflect MT protein levels and Cd appeared to bind to existing MT in the kidney. The results support the contention that MT protein levels often bear no clear relationship with mRNA levels and emphasizes the importance of measuring both in studies of MT expression.