Regulation of metallothionein isoform expression following induction by metals
The work described in this thesis reports the specificity of expression, and regulation of expression, of each rat MT isoform. Subcutaneous (sc) injection of 8.9 μmol/kg of cadmium (Cd) rapidly induced MT-1 (10-fold) and MT-2 (3-fold) total mRNAs in rat liver. However, at the peaks of the mRNA induction, not all the MT-2 mRNA was recruited into polyribosomes for translation, suggesting that there is post-transcriptional regulation of MT-2 expression. No evidence was found for such regulation of the MT-1 isoform. In rat kidneys, both isoform mRNAs were rapidly induced (10-fold) but there was no evidence for a similar induction of MT-protein, suggesting that there is post-transcriptional regulation of both MT isosforms in the kidneys. In both organs, metal analysis of digested tissues and gel chromatography/ICP-MS profiles indicated that there was an increase in Cd and Cd-Mt respectively. Subcutaneous (sc) injection of 8.7 μmol/kg of copper (Cu) rapidly induced both MT isoform mRNAs in liver. The extent of induction of total mRNA was higher for MT-2(30-fold) than for MT-1 (10-fold). As in the case of the Cd study, there was evidence for post-transcriptional regulation of MT-2 synthesis, but not of MT-1, according to analysis of polyribosomal mRNA. In the kidneys, there was no evidence for de novo synthesis of either MT mRNAs. However, there was a small induction of MT-protein. This may be explained by the transport of MT from other organs into the kidney under these treatment conditions. In both organs, an increase in Cu concentration and Cu-MT content was found.