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

Scott H. Garrett, Veronica Phillips, Seema Somji, Mary Ann Sens, Rana Dutta, Seongmi Park, Doyeob Kim, Donald A. Sens

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43 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)69-80
Number of pages12
JournalToxicology Letters
Issue number1
StatePublished - Jan 5 2002


  • Cadmium
  • Early response genes
  • Gene regulation
  • MT-3
  • Metallothionein
  • Nephropathy
  • Proximal tubule

ASJC Scopus subject areas

  • Toxicology


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