Abstract
Metallothioneins are encoded by a family of genes that are induced by inorganic mercury. Despite the well-characterized acute response of metallothionein (MT) genes in the kidneys and liver after a single exposure to inorganic mercury, relatively little is known about the activity of these genes and the content of MT protein during prolonged periods after exposure. Rats treated with inorganic mercury accumulate mercury rapidly in kidneys and liver during the first 24 h after exposure, but only in the kidneys does the content of mercury remain elevated throughout the initial 2 weeks. We report herein that transcription of MT genes in response to treatment with inorganic mercury differs dramatically between the kidneys and liver. MT gene transcription and levels of MT protein remained elevated in the kidneys throughout 14 days after treatment. In contrast, the initially high rates of MT gene transcription and enhanced content of MT protein in the liver fell to control levels by 14 days. In the liver, the rates of MTgene transcription and levels of MT protein were strongly correlated with each other and with the content of mercury. In the kidneys, however, these correlations were very weak or absent. Our data indicate that hepatic levels of MT protein are determined primarily byMT gene transcription, but that post-transcriptional events are important in determining the renal content of MT protein during the initial weeks after exposure. This has important implications in understanding differences in mechanisms controlling MT expression in the kidneys and liver.
Footnotes
-
Send reprint requests to: Dr. Rudolfs K. Zalups, Division of Basic Medical Sciences, Mercer University School of Medicine, 1550 College St., Macon, GA 31207-0001. E-mail: zalups.rk{at}gain.mercer.edu
-
↵1 This study was supported by grants awarded by the National Institute of Environmental Health Sciences (ES05157 and ES05980) and the Medical Research Council of Canada.
- Abbreviations:
- MT
- metallothionein
- DTT
- dithiothreitol
- GADPH
- glyceraldehyde phosphate dehydrogenase
- Received February 15, 2000.
- Accepted June 5, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
JPET articles become freely available 12 months after publication, and remain freely available for 5 years.Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page.
|