Mice exposed in situ to urban air pollution exhibit pulmonary alterations in gene expression in the lipid droplet synthesis pathways

Environmental and Molecular Mutagenesis - Tập 54 Số 4 - Trang 240-249 - 2013
Andrea Rowan‐Carroll1, Sabina Halappanavar1, Andrew Williams1, Christophers M. Somers2, Carole L. Yauk1
1Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada
2Department of Biology; University of Regina; Saskatchewan; Canada

Tóm tắt

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,andAgpat2), 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. Environ. Mol. Mutagen. 54:240–249, 2013. © 2013 Wiley Periodicals, Inc.

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Tài liệu tham khảo

10.1074/jbc.M111.250449

10.1002/ajim.20337

10.2105/AJPH.79.5.623

10.1016/j.jhazmat.2010.06.120

10.2337/db07-1383

10.1165/ajrcmb.25.4.4515

10.1093/toxsci/kfs119

10.1007/s004200050319

10.1038/ng1201-365

10.1152/ajpgi.00566.2006

10.1093/biostatistics/kxh018

10.4049/jimmunol.0903475

10.1074/jbc.M208262200

Environment Canada EPS Environmental Technology Advancement Directorate PMD Environmental Technology Centre O Ontario.2004. National air pollution surveillance network quality assurance and quality control guidelines. Report No. AAQD2004–1.

10.1152/ajpendo.00646.2009

10.1186/1755-8794-2-56

10.1016/j.tox.2011.04.011

Hochberg YBaY, 1995, Controlling the false discovery rate: A practical and powerful approach to multiple testing, J R Stat Soc Ser B (Methodological), 57, 289, 10.1111/j.2517-6161.1995.tb02031.x

IARC.1987.Overall evaluations of carcinogenicity: An updating of IARC monographs Volumes 1 to 42. IARC monographs on the evaluation of carcinogenic risks to humans supplement/World Health Organization.International Agency for Research on Cancer (IARC)1-42:1–440.

10.2337/dc11-s250

10.1017/S0016672308009713

10.1016/j.bbalip.2012.01.001

10.1016/j.taap.2009.05.010

10.1007/s00420-007-0178-z

10.1289/ehp.6000

10.1080/10473289.2006.10464461

10.1038/nrm1912

10.1007/978-1-4613-8122-8

10.1289/ehp.7898

10.1165/rcmb.2007-0204OC

10.1126/science.1108752

10.1289/ehp.98106189

10.1016/j.bpc.2011.06.009

10.1511/2007.65.232

10.1126/science.1095815

10.1007/s00420-001-0305-1

10.1021/nn101492k

Team TRDC.2010.R: A language and environment for statistical computing Version 2.11.0.

10.1146/annurev-biochem-061009-102430

Wu H, 2003, Maanova: A Software Package for the Analysis of Spotted cDNA Microarray Experiments in the Analysis of Gene Expression Data: An Overview of Methods and Software

10.1093/nar/30.4.e15

10.1073/pnas.0705896105

10.1002/em.20290

10.1002/em.21689

10.1194/jlr.R800018-JLR200