TY - JOUR
T1 - Transcriptome-wide analyses indicate mitochondrial responses to particulate air pollution exposure
AU - Winckelmans, Ellen
AU - Nawrot, Tim S.
AU - Tsamou, Maria
AU - Den Hond, Elly
AU - Baeyens, Willy
AU - Kleinjans, Jos
AU - Lefebvre, Wouter
AU - Van Larebeke, Nicolas
AU - Peusens, Martien
AU - Plusquin, Michelle
AU - Reynders, Hans
AU - Schoeters, Greet
AU - Vanpoucke, Charlotte
AU - De Kok, Theo M.
AU - Vrijens, Karen
PY - 2017/8/18
Y1 - 2017/8/18
N2 - 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.
AB - 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.
KW - Ambient air pollution
KW - Particulate matter
KW - Sex-specific, mitochondria
KW - Transcriptome-wide analyses
KW - Air Pollutants/toxicity
KW - Environmental Monitoring
KW - Genes, Mitochondrial/drug effects
KW - Humans
KW - Middle Aged
KW - Male
KW - Gene Expression Profiling
KW - Environmental Exposure
KW - Belgium
KW - Sex Factors
KW - Transcriptome/drug effects
KW - Female
KW - Aged
KW - Particulate Matter/toxicity
KW - Real-Time Polymerase Chain Reaction
KW - Cohort Studies
U2 - 10.1186/s12940-017-0292-7
DO - 10.1186/s12940-017-0292-7
M3 - Journal article
C2 - 28821289
AN - SCOPUS:85027519108
SN - 1476-069X
VL - 16
JO - Environmental Health
JF - Environmental Health
M1 - 87
ER -