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

Environmental Health

Charlotte Vanpoucke¹  Ellen Winckelmans²  Martien Peusens²  Michelle Plusquin²  Maria Tsamou²  Tim S Nawrot²  Karen Vrijens²  Willy Baeyens³  Nicolas Van Larebeke⁴  Jos Kleinjans⁵  Theo M de Kok⁵  Hans Reynders⁶  Wouter Lefebvre⁷  Greet Schoeters⁷  Elly Den Hond⁸ 

[1] Belgian Interregional Environment Agency (IRCEL);Centre for Environmental Sciences, Hasselt University;Department of Analytical and Environmental Chemistry, Vrije Universiteit Brussel;Department of Radiotherapy and Nuclear Medicine, Ghent University;Department of Toxicogenomics, Maastricht University;Environment, Nature and Energy Department, Flemish Government;Flemish Institute for Technological Research;Provincial Institute for Hygiene;

关键词: Ambient air pollution;    Particulate matter;    Transcriptome-wide analyses;    Sex-specific, mitochondria;   

DOI  :  10.1186/s12940-017-0292-7

来源: DOAJ

【 摘 要 】

Abstract 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 PM10 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) PM10 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 PM10 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.

【 授权许可】

Unknown