Differential expression of human metallothionein isoform I mRNA in human proximal tubule cells exposed to metals.
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.
Garrett
S H
SH
Robert C. Byrd Health Sciences Center, Department of Pathology, West Virginia University, Morgantown, WV 26506 USA.
Somji
S
S
Todd
J H
JH
Sens
M A
MA
Sens
D A
DA
D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D020440:Gene Duplication; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000187:drug effects* / Q000378:metabolism; D008668:Metallothionein / Q000187:drug effects / Q000235:genetics*; D019216:Metals, Heavy / Q000494:pharmacology / Q000633:toxicity*; D012333:RNA, Messenger / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019216:Metals, Heavy; D012333:RNA, Messenger; D008668:Metallothionein