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Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure

BACKGROUND: Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM(10) exposure. METHODS: Whole genome gene expression was measured in peripheral blood of 98 adu...

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Autores principales: Winckelmans, Ellen, Nawrot, Tim S, Tsamou, Maria, Den Hond, Elly, Baeyens, Willy, Kleinjans, Jos, Lefebvre, Wouter, Van Larebeke, Nicolas, Peusens, Martien, Plusquin, Michelle, Reynders, Hans, Schoeters, Greet, Vanpoucke, Charlotte, de Kok, Theo M, Vrijens, Karen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563023/
https://www.ncbi.nlm.nih.gov/pubmed/28821289
http://dx.doi.org/10.1186/s12940-017-0292-7
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author Winckelmans, Ellen
Nawrot, Tim S
Tsamou, Maria
Den Hond, Elly
Baeyens, Willy
Kleinjans, Jos
Lefebvre, Wouter
Van Larebeke, Nicolas
Peusens, Martien
Plusquin, Michelle
Reynders, Hans
Schoeters, Greet
Vanpoucke, Charlotte
de Kok, Theo M
Vrijens, Karen
author_facet Winckelmans, Ellen
Nawrot, Tim S
Tsamou, Maria
Den Hond, Elly
Baeyens, Willy
Kleinjans, Jos
Lefebvre, Wouter
Van Larebeke, Nicolas
Peusens, Martien
Plusquin, Michelle
Reynders, Hans
Schoeters, Greet
Vanpoucke, Charlotte
de Kok, Theo M
Vrijens, Karen
author_sort Winckelmans, Ellen
collection PubMed
description BACKGROUND: Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM(10) exposure. METHODS: Whole genome gene expression was measured in peripheral blood of 98 adults (49% women). We performed linear regression analyses stratified by sex and adjusted for individual and temporal characteristics to investigate alterations in gene expression induced by short-term (week before blood sampling) and medium-term (month before blood sampling) PM(10) exposure. Overrepresentation analyses (ConsensusPathDB) were performed to identify enriched mitochondrial associated pathways and gene ontology sets. Thirteen Human MitoCarta genes were measured by means of quantitative real-time polymerase chain reaction (qPCR) along with mitochondrial DNA (mtDNA) content in an independent validation cohort (n = 169, 55.6% women). RESULTS: Overrepresentation analyses revealed significant pathways (p-value <0.05) related to mitochondrial genome maintenance and apoptosis for short-term exposure and to the electron transport chain (ETC) for medium-term exposure in women. For men, medium-term PM(10) exposure was associated with the Tri Carbonic Acid cycle. In an independent study population, we validated several ETC genes, including UQCRH and COX7C (q-value <0.05), and some genes crucial for the maintenance of the mitochondrial genome, including LONP1 (q-value: 0.07) and POLG (q-value: 0.04) in women. CONCLUSIONS: In this exploratory study, we identified mitochondrial genes and pathways associated with particulate air pollution indicating upregulation of energy producing pathways as a potential mechanism to compensate for PM-induced mitochondrial damage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-017-0292-7) contains supplementary material, which is available to authorized users.
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spelling pubmed-55630232017-08-21 Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure Winckelmans, Ellen Nawrot, Tim S Tsamou, Maria Den Hond, Elly Baeyens, Willy Kleinjans, Jos Lefebvre, Wouter Van Larebeke, Nicolas Peusens, Martien Plusquin, Michelle Reynders, Hans Schoeters, Greet Vanpoucke, Charlotte de Kok, Theo M Vrijens, Karen Environ Health Research BACKGROUND: Due to their lack of repair capacity mitochondria are critical targets for environmental toxicants. We studied genes and pathways reflecting mitochondrial responses to short- and medium-term PM(10) exposure. METHODS: Whole genome gene expression was measured in peripheral blood of 98 adults (49% women). We performed linear regression analyses stratified by sex and adjusted for individual and temporal characteristics to investigate alterations in gene expression induced by short-term (week before blood sampling) and medium-term (month before blood sampling) PM(10) exposure. Overrepresentation analyses (ConsensusPathDB) were performed to identify enriched mitochondrial associated pathways and gene ontology sets. Thirteen Human MitoCarta genes were measured by means of quantitative real-time polymerase chain reaction (qPCR) along with mitochondrial DNA (mtDNA) content in an independent validation cohort (n = 169, 55.6% women). RESULTS: Overrepresentation analyses revealed significant pathways (p-value <0.05) related to mitochondrial genome maintenance and apoptosis for short-term exposure and to the electron transport chain (ETC) for medium-term exposure in women. For men, medium-term PM(10) exposure was associated with the Tri Carbonic Acid cycle. In an independent study population, we validated several ETC genes, including UQCRH and COX7C (q-value <0.05), and some genes crucial for the maintenance of the mitochondrial genome, including LONP1 (q-value: 0.07) and POLG (q-value: 0.04) in women. CONCLUSIONS: In this exploratory study, we identified mitochondrial genes and pathways associated with particulate air pollution indicating upregulation of energy producing pathways as a potential mechanism to compensate for PM-induced mitochondrial damage. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12940-017-0292-7) contains supplementary material, which is available to authorized users. BioMed Central 2017-08-18 /pmc/articles/PMC5563023/ /pubmed/28821289 http://dx.doi.org/10.1186/s12940-017-0292-7 Text en © The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Winckelmans, Ellen
Nawrot, Tim S
Tsamou, Maria
Den Hond, Elly
Baeyens, Willy
Kleinjans, Jos
Lefebvre, Wouter
Van Larebeke, Nicolas
Peusens, Martien
Plusquin, Michelle
Reynders, Hans
Schoeters, Greet
Vanpoucke, Charlotte
de Kok, Theo M
Vrijens, Karen
Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
title Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
title_full Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
title_fullStr Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
title_full_unstemmed Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
title_short Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
title_sort transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5563023/
https://www.ncbi.nlm.nih.gov/pubmed/28821289
http://dx.doi.org/10.1186/s12940-017-0292-7
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