| Differential Expression of Human Metallothionein Isoform I mRNA in Human Proximal Tubule Cells Exposed to Metals Scott H. Garrett, Seema Somji, John H. Todd, Mary Ann Sens, and Donald A. Sens Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia University, Morgantown, WV 26506 USA Abstract
In contrast to the single metallothionein (MT) -1 gene of the mouse, the human MT-1 gene family is composed of seven active genes and six pseudogenes. In this study, the expression of mRNA representing the seven active human MT-1 genes was determined in cultured human proximal tubule (HPT) cells under basal conditions and after exposure to the metals Cd2+, Zn2+, Cu2+, Hg2+, Ag2+, and Pb2+. Basal expression of MT-1X and MT-1E mRNA in HPT cells was similar to expression of the housekeeping gene glyceraldehyde 3-phosphate dehydrogenase. In contrast, mRNAs representing the basal expression of MT-1A and MT-1F were a minor transcript in HPT cells. Treatment of HPT cells with Cd2+, Zn2+, or Cu2+ increased the levels of MT-1E and MT-1A mRNA, but not the levels of MT-1X or MT-1F mRNA. The increase in MT-1E mRNA appeared to be influenced mainly by exposure to the various metals, whereas the increase in MT-1A mRNA was influenced more by exposure to a metal concentration eliciting a loss of cell viability. Treatment of HPT cells with the metals Hg2+, Ag2+, and Pb2+ was found to have no effect on the level of MT-1 mRNA at either sublethal or lethal concentrations. Using HPT cells as a model, these results suggest that new features of MT gene expression have been acquired in the human due to the duplication of the MT-1 gene. Key words: cadmium, copper, gene expression, heavy metals, lead, mercury, metallothionein, mRNA, proximal tubule, RT-PCR, reverse transcriptase-polymerase chain reaction, silver, zinc. Environ Health Perspect 106:825-832 (1998) . [Online 17 November 1998] http://ehpnet1.niehs.nih.gov/docs/1998/106p825-832garrett/ abstract.html Address correspondence to D.A. Sens, Department of Pathology, West Virginia University, P.O. Box 9203, Morgantown, WV 26506-9203. This publication was made possible by grant number ESO7687 from the National Institute of Environmental Health Sciences. Received 3 June 1998 ; accepted 4 August 1998.
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