Transient induction of metallothionein isoform 3 (MT-3), c-fos, c-jun and c-myc in human proximal tubule cells exposed to cadmium.

Cadmium (Cd(+2)) has been shown to transiently increase the expression of mRNA for the third isoform of the metallothionein (MT-3) gene family in cultured human proximal tubule (HPT) cells. The goal of the present study was to further define the expression of MT-3 in mortal (HPT) and immortal (HK-2) cultures of HPT cells when exposed to lethal and sub-lethal concentrations of Cd(+2) under both acute and chronic time periods of exposure. Expression of MT-3 mRNA and protein was determined in cultured HPT cells and HK-2 cells using reverse-transcription-polymerase chain reaction (RT-PCR) and immuno-blotting, and expression of c-fos, c-jun and c-myc mRNA by RT-PCR. The results confirmed that exposure of the HPT cells to Cd(+2) induced a transient increase in MT-3 mRNA and extended the induction to include a subsequent transient increase in the level of the MT-3 protein. The induction of MT-3 was rapid and returned to control values within 48 h of exposure despite the continued presence of lethal and sublethal concentrations of Cd(+2). It was also demonstrated that the pattern of expression of MT-3 mRNA was similar to that of the early response genes, c-fos, c-jun and c-myc. It was shown that the HK-2 cells did not express MT-3 when exposed to Cd(+2), but had similar expression of the c-fos, c-jun and c-myc genes. The results demonstrate that MT-3 expression is metal responsive in HPT cells.