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Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity

BACKGROUND: Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. RESULTS: Using Caenorhabditis elegans, 290 genes were identifie...

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Autores principales: Cui, Yuxia, McBride, Sandra J, Boyd, Windy A, Alper, Scott, Freedman, Jonathan H
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394766/
https://www.ncbi.nlm.nih.gov/pubmed/17592649
http://dx.doi.org/10.1186/gb-2007-8-6-r122
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author Cui, Yuxia
McBride, Sandra J
Boyd, Windy A
Alper, Scott
Freedman, Jonathan H
author_facet Cui, Yuxia
McBride, Sandra J
Boyd, Windy A
Alper, Scott
Freedman, Jonathan H
author_sort Cui, Yuxia
collection PubMed
description BACKGROUND: Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. RESULTS: Using Caenorhabditis elegans, 290 genes were identified that are differentially expressed (>1.5-fold) following a 4 or 24 hour exposure to cadmium. Several of these genes are known to be involved in metal detoxification, including mtl-1, mtl-2, cdr-1 and ttm-1, confirming the efficacy of the study. The majority, however, were not previously associated with metal-responsiveness and are novel. Gene Ontology analysis mapped these genes to cellular/ion trafficking, metabolic enzymes and proteolysis categories. RNA interference-mediated inhibition of 50 cadmium-responsive genes resulted in an increased sensitivity to cadmium toxicity, demonstrating that these genes are involved in the resistance to cadmium toxicity. Several functional protein interacting networks were identified by interactome analysis. Within one network, the signaling protein KEL-8 was identified. Kel-8 protects C. elegans from cadmium toxicity in a mek-1 (MAPKK)-dependent manner. CONCLUSION: Because many C. elegans genes and signal transduction pathways are evolutionarily conserved, these results may contribute to the understanding of the functional roles of various genes in cadmium toxicity in higher organisms.
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spelling pubmed-23947662008-05-24 Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity Cui, Yuxia McBride, Sandra J Boyd, Windy A Alper, Scott Freedman, Jonathan H Genome Biol Research BACKGROUND: Exposure to cadmium is associated with a variety of human diseases. At low concentrations, cadmium activates the transcription of stress-responsive genes, which can prevent or repair the adverse effects caused by this metal. RESULTS: Using Caenorhabditis elegans, 290 genes were identified that are differentially expressed (>1.5-fold) following a 4 or 24 hour exposure to cadmium. Several of these genes are known to be involved in metal detoxification, including mtl-1, mtl-2, cdr-1 and ttm-1, confirming the efficacy of the study. The majority, however, were not previously associated with metal-responsiveness and are novel. Gene Ontology analysis mapped these genes to cellular/ion trafficking, metabolic enzymes and proteolysis categories. RNA interference-mediated inhibition of 50 cadmium-responsive genes resulted in an increased sensitivity to cadmium toxicity, demonstrating that these genes are involved in the resistance to cadmium toxicity. Several functional protein interacting networks were identified by interactome analysis. Within one network, the signaling protein KEL-8 was identified. Kel-8 protects C. elegans from cadmium toxicity in a mek-1 (MAPKK)-dependent manner. CONCLUSION: Because many C. elegans genes and signal transduction pathways are evolutionarily conserved, these results may contribute to the understanding of the functional roles of various genes in cadmium toxicity in higher organisms. BioMed Central 2007 2007-06-25 /pmc/articles/PMC2394766/ /pubmed/17592649 http://dx.doi.org/10.1186/gb-2007-8-6-r122 Text en Copyright © 2007 Cui et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an open access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research
Cui, Yuxia
McBride, Sandra J
Boyd, Windy A
Alper, Scott
Freedman, Jonathan H
Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
title Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
title_full Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
title_fullStr Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
title_full_unstemmed Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
title_short Toxicogenomic analysis of Caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
title_sort toxicogenomic analysis of caenorhabditis elegans reveals novel genes and pathways involved in the resistance to cadmium toxicity
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2394766/
https://www.ncbi.nlm.nih.gov/pubmed/17592649
http://dx.doi.org/10.1186/gb-2007-8-6-r122
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