title: Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene expression in the lipid droplet synthesis pathways.
abstract: It is clear that particulate air pollution poses a serious risk to human health; however, the underlying mechanisms are not completely understood. We investigated pulmonary transcriptional responses in mice following in-situ exposure to ambient air in a heavily industrialized urban environment. Mature C57BL/CBA male mice were caged in sheds near two working steel mills and a major highway in Hamilton, Ontario, Canada in the spring/summer of 2004. Control mice were housed in the same environment, but received only high-efficiency particle filtered air (HEPA). Whole lung tissues were collected from mice exposed for 3, 10, or for 10 weeks followed by 6 weeks recovery in the laboratory (16 weeks). DNA microarrays were used to profile changes in pulmonary gene expression. Transcriptional profiling revealed changes in the expression of genes implicated in the lipid droplet synthesis (Plin I, Dgat2, Lpl, S3-12, and Agpat2), and antioxidant defense (Ucp1) pathways in mice breathing unfiltered air. We postulate that exposure to urban air, containing an abundance of particulate matter adsorbed with polycyclic aromatic hydrocarbons, triggers lipid droplet (holding depots for lipids and malformed/excess proteins tagged for degradation) synthesis in the lungs, which may act to sequester particulates. Increased lipid droplet synthesis could lead to endogenous/stressor-induced production of reactive oxygen species and activation of antioxidant mechanisms. Further investigation into the stimulation of lipid droplet synthesis in the lung in response to air pollution and the resulting health implications is warranted.
authors.affiliation: Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.
authors.forename: Andrea
authors.initials: A
authors.lastname: Rowan-Carroll
authors.forename: Sabina
authors.initials: S
authors.lastname: Halappanavar
authors.forename: Andrew
authors.initials: A
authors.lastname: Williams
authors.forename: Christophers M
authors.initials: CM
authors.lastname: Somers
authors.forename: Carole L
authors.initials: CL
authors.lastname: Yauk
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000397:Air Pollution; D000818:Animals; D053898:Biosynthetic Pathways / Q000235:genetics*; D018736:DNA Adducts / Q000378:metabolism; D053960:DNA Breaks; D006801:Humans; D007220:Industrial Waste; D050356:Lipid Metabolism / Q000187:drug effects / Q000235:genetics; D008168:Lung / Q000187:drug effects / Q000378:metabolism*; D008171:Lung Diseases / Q000139:chemically induced; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D009864:Ontario; D052638:Particulate Matter / Q000633:toxicity*; D060888:Real-Time Polymerase Chain Reaction; D013094:Spermatozoa / Q000187:drug effects; D059467:Transcriptome / Q000187:drug effects*; D014505:Urban Population
chemical_list: D000393:Air Pollutants; D018736:DNA Adducts; D007220:Industrial Waste; D052638:Particulate Matter