Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.

Cobalt is a transition group metal present in trace amounts in the human diet, but in larger doses it can be acutely toxic or cause adverse health effects in chronic exposures. Its use in many industrial processes and alloys worldwide presents opportunities for occupational exposures, including mili...

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Main Authors: Matthew G Permenter, William E Dennis, Thomas E Sutto, David A Jackson, John A Lewis, Jonathan D Stallings
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2013-01-01
Series:PLoS ONE
Online Access:http://europepmc.org/articles/PMC3875483?pdf=render
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spelling doaj-4fef0b99490442dc9bde9e4102ebd65e2020-11-24T21:16:20ZengPublic Library of Science (PLoS)PLoS ONE1932-62032013-01-01812e8375110.1371/journal.pone.0083751Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.Matthew G PermenterWilliam E DennisThomas E SuttoDavid A JacksonJohn A LewisJonathan D StallingsCobalt is a transition group metal present in trace amounts in the human diet, but in larger doses it can be acutely toxic or cause adverse health effects in chronic exposures. Its use in many industrial processes and alloys worldwide presents opportunities for occupational exposures, including military personnel. While the toxic effects of cobalt have been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify potential biomarkers of exposure or effect, we exposed two rat liver-derived cell lines, H4-II-E-C3 and MH1C1, to two concentrations of cobalt chloride. We examined changes in gene expression using DNA microarrays in both cell lines and examined changes in cytoplasmic protein abundance in MH1C1 cells using mass spectrometry. We chose to closely examine differentially expressed genes and proteins changing in abundance in both cell lines in order to remove cell line specific effects. We identified enriched pathways, networks, and biological functions using commercial bioinformatic tools and manual annotation. Many of the genes, proteins, and pathways modulated by exposure to cobalt appear to be due to an induction of a hypoxic-like response and oxidative stress. Genes that may be differentially expressed due to a hypoxic-like response are involved in Hif-1α signaling, glycolysis, gluconeogenesis, and other energy metabolism related processes. Gene expression changes linked to oxidative stress are also known to be involved in the NRF2-mediated response, protein degradation, and glutathione production. Using microarray and mass spectrometry analysis, we were able to identify modulated genes and proteins, further elucidate the mechanisms of toxicity of cobalt, and identify biomarkers of exposure and effect in vitro, thus providing targets for focused in vivo studies.http://europepmc.org/articles/PMC3875483?pdf=render
collection DOAJ
language English
format Article
sources DOAJ
author Matthew G Permenter
William E Dennis
Thomas E Sutto
David A Jackson
John A Lewis
Jonathan D Stallings
spellingShingle Matthew G Permenter
William E Dennis
Thomas E Sutto
David A Jackson
John A Lewis
Jonathan D Stallings
Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
PLoS ONE
author_facet Matthew G Permenter
William E Dennis
Thomas E Sutto
David A Jackson
John A Lewis
Jonathan D Stallings
author_sort Matthew G Permenter
title Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
title_short Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
title_full Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
title_fullStr Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
title_full_unstemmed Exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
title_sort exposure to cobalt causes transcriptomic and proteomic changes in two rat liver derived cell lines.
publisher Public Library of Science (PLoS)
series PLoS ONE
issn 1932-6203
publishDate 2013-01-01
description Cobalt is a transition group metal present in trace amounts in the human diet, but in larger doses it can be acutely toxic or cause adverse health effects in chronic exposures. Its use in many industrial processes and alloys worldwide presents opportunities for occupational exposures, including military personnel. While the toxic effects of cobalt have been widely studied, the exact mechanisms of toxicity remain unclear. In order to further elucidate these mechanisms and identify potential biomarkers of exposure or effect, we exposed two rat liver-derived cell lines, H4-II-E-C3 and MH1C1, to two concentrations of cobalt chloride. We examined changes in gene expression using DNA microarrays in both cell lines and examined changes in cytoplasmic protein abundance in MH1C1 cells using mass spectrometry. We chose to closely examine differentially expressed genes and proteins changing in abundance in both cell lines in order to remove cell line specific effects. We identified enriched pathways, networks, and biological functions using commercial bioinformatic tools and manual annotation. Many of the genes, proteins, and pathways modulated by exposure to cobalt appear to be due to an induction of a hypoxic-like response and oxidative stress. Genes that may be differentially expressed due to a hypoxic-like response are involved in Hif-1α signaling, glycolysis, gluconeogenesis, and other energy metabolism related processes. Gene expression changes linked to oxidative stress are also known to be involved in the NRF2-mediated response, protein degradation, and glutathione production. Using microarray and mass spectrometry analysis, we were able to identify modulated genes and proteins, further elucidate the mechanisms of toxicity of cobalt, and identify biomarkers of exposure and effect in vitro, thus providing targets for focused in vivo studies.
url http://europepmc.org/articles/PMC3875483?pdf=render
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