Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines

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 geno...

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Autores principales: ARMENDÁRIZ,ÁNGELA D, OLIVARES,FELIPE, PULGAR,RODRIGO, LOGUINOV,ALEX, CAMBIAZO,VERÓNICA, VULPE,CHRISTOPHER D, GONZÁLEZ,MAURICIO
Lenguaje:English
Publicado: Sociedad de Biología de Chile 2006
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Acceso en línea:http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000100015
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spelling oai:scielo:S0716-976020060001000152006-06-30Gene expression profiling in wild-type and metallothionein mutant fibroblast cell linesARMENDÁRIZ,ÁNGELA DOLIVARES,FELIPEPULGAR,RODRIGOLOGUINOV,ALEXCAMBIAZO,VERÓNICAVULPE,CHRISTOPHER DGONZÁLEZ,MAURICIO copper homeostasis metallothionein microarray 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.info:eu-repo/semantics/openAccessSociedad de Biología de ChileBiological Research v.39 n.1 20062006-01-01text/htmlhttp://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000100015en10.4067/S0716-97602006000100015
institution Scielo Chile
collection Scielo Chile
language English
topic copper homeostasis
metallothionein
microarray
spellingShingle copper homeostasis
metallothionein
microarray
ARMENDÁRIZ,ÁNGELA D
OLIVARES,FELIPE
PULGAR,RODRIGO
LOGUINOV,ALEX
CAMBIAZO,VERÓNICA
VULPE,CHRISTOPHER D
GONZÁLEZ,MAURICIO
Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines
description 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.
author ARMENDÁRIZ,ÁNGELA D
OLIVARES,FELIPE
PULGAR,RODRIGO
LOGUINOV,ALEX
CAMBIAZO,VERÓNICA
VULPE,CHRISTOPHER D
GONZÁLEZ,MAURICIO
author_facet ARMENDÁRIZ,ÁNGELA D
OLIVARES,FELIPE
PULGAR,RODRIGO
LOGUINOV,ALEX
CAMBIAZO,VERÓNICA
VULPE,CHRISTOPHER D
GONZÁLEZ,MAURICIO
author_sort ARMENDÁRIZ,ÁNGELA D
title Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines
title_short Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines
title_full Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines
title_fullStr Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines
title_full_unstemmed Gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines
title_sort gene expression profiling in wild-type and metallothionein mutant fibroblast cell lines
publisher Sociedad de Biología de Chile
publishDate 2006
url http://www.scielo.cl/scielo.php?script=sci_arttext&pid=S0716-97602006000100015
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