Exposure of human proximal tubule cells to cytotoxic levels of CdCl 2 induces the additional expression of metallothionein 1A mRNA

Abstract

Humans, in contrast to animals, have a complex expression of metallothionein (MT) genes which involves many MT isoforms encoded by a family of genes containing an upper limit of 12 possible functional genes. It is unknown if these human isoforms of MT have distinct functions or if they simply represent a non-essential duplication of gene function. In the present study, MT protein and mRNA for the MT-2A, MT-1A, B, E, F, and G genes was determined for 3 isolates of human proximal tubule (HPT) cells having distinct sensitivities to cadmium. For all 3 HPT isolates, the expression of MT protein and mRNA for the MT-2A, MT-1E, MT-1F and MT-1G isoforms was similar among the isolates and demonstrated no correlation to lethality. However, each isoform mRNA was expressed at different levels when compared to one another. In contrast, the expression of MT-1A mRNA differed in expression and correlated with the differing lethalities displayed by each isolate. The finding of different profiles of mRNA expression provides evidence that the MT isoforms may have unique functions and that mRNA for the MT-1A gene could be a potential marker for heavy metal exposure and/or toxicity.