| Abstract | dc.description.abstract | The role of metallothioneins (MT) in copper homeostasis is of great interest, as it appears to be partially
responsible for the regulation of intracellular copper levels during adaptation to extracellular excess of the
metal. To further investigate a possible role of MTs in copper metabolism, a genomics approach was utilized
to evaluate the role of MT on gene expression. Microarray analysis was used to examine the effects of copper
overload in fibroblast cells from normal and MT I and II double knock-out mice (MT-/-). As a first step, we
compared genes that were significantly upregulated in wild-type and MT-/- cells exposed to copper. Even
though wild-type and mutant cells are undistinguishable in terms of their morphological features and rates of
growth, our results show that MT-/- cells do not respond with induction of typical markers of cellular stress
under copper excess conditions, as observed in the wild-type cell line, suggesting that the transcription
initiation rate or the mRNA stability of stress genes is affected when there is an alteration in the copper store
capacity. The functional classification of other up-regulated genes in both cell lines indicates that a large
proportion (>80%) belong to two major categories: 1) metabolism; and 2) cellular physiological processes,
suggesting that at the transcriptional level copper overload induces the expression of genes associated with
diverse molecular functions. These results open the possibility to understand how copper homeostasis is being
coordinated with other metabolic pathways. | en |
