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

• Published in: Environmental Health
• Main Authors: 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
• Format: Article in Journal/Newspaper
• Language: English
• Published: 2017
• Subjects: Ambient air pollution; Particulate matter; Sex-specific; mitochondria; Transcriptome-wide analyses; Air Pollutants/toxicity; Environmental Monitoring; Genes; Mitochondrial/drug effects; Humans; Middle Aged; Male; Gene Expression Profiling; Environmental Exposure; Belgium; Sex Factors; Transcriptome/drug effects; Female; Aged; Particulate Matter/toxicity; Real-Time Polymerase Chain Reaction; Cohort Studies; Carbonic acid
• Online Access: https://portal.findresearcher.sdu.dk/da/publications/94276035-dfcf-43dc-918b-f32d95639241; https://doi.org/10.1186/s12940-017-0292-7; https://findresearcher.sdu.dk/ws/files/135405458/Transcriptome_wide_analyses_indicate_mitochondrial_responses_to_particulate_air_pollution_exposure.pdf

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.