Decreased PM10 exposure attenuates age-related lung function decline: genetic variants in p53, p21, and CCND1 modify this effect
| Autor: | Imboden Medea, Schwartz Joel, Schindler Christian, Curjuric Ivan, Berger Wolfgang, Liu Sally L J, Russi Erich W, Ackermann-Liebrich Ursula, Rochat Thierry, Probst-Hensch Nicole M, SAPALDIA Team |
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| Přispěvatelé: | SAPALDIA, Team, Ackermann-Liebrich, U., Gaspoz, JM., Leuenberger, P., Liu, LJ., Probst-Hensch, NM., Schindler, C., Rochat, T., Barthélémy, JC., Berger, W., Bettschart, R., Bircher, A., Bolognini, G., Brändli, O., Brutsche, M., Burdet, L., Frey, M., Gerbase, MW., Gold, D., Karrer, W., Keller, R., Knöpfli, B., Künzli, N., Neu, U., Nicod, L., Pons, M., Russi, E., Schmid-Grendelmeyer, P., Schwartz, J., Straehl, P., Tschopp, JM., von Eckardstein, A., Zellweger, JP., Zemp Stutz, E., Bridevaux, PO., Curjuric, I., Dratva, J., Felber Dietrich, D., Keidel, D., Imboden, M., Phuleria, H., Schaffner, E., Thun, GA., University of Zurich, Probst-Hensch, N M |
| Rok vydání: | 2009 |
| Předmět: |
Male
Health Toxicology and Mutagenesis air pollution Air Pollutants/*toxicity Cohort Studies 11124 Institute of Medical Molecular Genetics 0302 clinical medicine Genes p53 540 Chemistry Cyclin D1 Respiratory function Respiratory system genes Lung 10038 Institute of Clinical Chemistry ddc:616 Air Pollutants 0303 health sciences education.field_of_study respiratory function tests Cell cycle Genetic Variation Respiratory Function Tests 3. Good health medicine.anatomical_structure cell cycle Female Adult medicine.medical_specialty Air Pollutants/toxicity Base Sequence Cyclin D1/genetics DNA Primers Humans Lung/drug effects Lung/physiology Particle Size Proto-Oncogene Proteins p21(ras)/genetics Population 610 Medicine & health Context (language use) Biology Proto-Oncogene Proteins p21(ras) 03 medical and health sciences FEV1/FVC ratio Internal medicine 2307 Health Toxicology and Mutagenesis cohort study medicine education 030304 developmental biology Research Public Health Environmental and Occupational Health 10060 Epidemiology Biostatistics and Prevention Institute (EBPI) 2739 Public Health Environmental and Occupational Health Proto-Oncogene Proteins p21(ras)/*genetics Cyclin D1/*genetics Endocrinology Lung/*drug effects/physiology 030228 respiratory system 13. Climate action Immunology 570 Life sciences biology |
| Zdroj: | Environmental health perspectives Environmental Health Perspectives Environmental Health Perspectives, Vol. 117, No 9 (2009) pp. 1420-1427 Environmental Health Perspectives, vol. 117, no. 9, pp. 1420-1427 |
| ISSN: | 0091-6765 |
| DOI: | 10.1289/ehp.0800430 |
| Popis: | A large body of evidence underscores the adverse effect of long-term exposure to ambient particulate matter (PM) air pollution on respiratory health (Brunekreef and Forsberg 2005; Gotschi et al. 2008). Among adults in Switzerland, we have previously demonstrated cross-sectionally that residents of more polluted areas have lower lung function (Ackermann-Liebrich et al. 1997). More recently, we presented evidence from the same population-based cohort [Swiss Cohort Study on Air Pollution and Lung and Heart Diseases in Adults (SAPALDIA)] that decreasing exposure to airborne PM attenuated the average age-related decline in lung function. The associations were strongest for respiratory function tests reflecting small-airway function, namely, FEF25–75 [forced expiratory flow between 25% and 75% of forced vital capacity (FVC)] (Downs et al. 2007). Similar results from studies following interventions such as building bypasses for congested traffic routes (Burr et al. 2004; Hedley et al. 2002) or banning environmental tobacco smoke (ETS) exposure (Goodman et al. 2007; Menzies et al. 2006) showed that the improvements in air quality were accompanied by a decrease in cardiopulmonary mortality and an improvement in respiratory symptoms and lung function. However, it is still unknown whether all subjects benefit equally from a reduction in air pollution. Variation in genes mediating the pathobiological effect of air pollution in the lung may codetermine the degree to which a person benefits from better air quality. Experimental evidence indicates that PM alters expression of tumor protein gene p53, cyclin-dependent kinase inhibitor 1A gene (p21), and the cyclin D1 gene (CCND1) and subsequently affects cell proliferation and apoptosis of lung fibroblasts, lymphocytes, and alveolar epithelial cells (Bayram et al. 2006; Dagher et al. 2006; Nyunoya et al. 2006; Rosas Perez et al. 2007; Soberanes et al. 2006). PM is furthermore well known to induce oxidative stress in the airways (Li et al. 2008). In fact, the expression of all three gene candidates, p53, p21, and CCND1, in bronchial epithelial cells and lung fibroblasts seems to be regulated in part by redox-dependent mechanisms (Jiao et al. 2008; Ranjan et al. 2006; Yao et al. 2008). The tumor suppressor p53, a nuclear transcription factor, binds to response elements in the promoter region of many genes and plays a pivotal role in apoptosis. It induces up-regulation of the expression of many pro-apoptotic genes and down-regulation of anti-apoptotic genes (Oren et al. 2002). CCND1 (cyclin D1) is known to promote cell proliferation through cell cycle G1–S phase transition. The protein p21 (also known as Waf1 or Cip1) is a direct functional counterpart of CCND1 and an important downstream effector of p53 action that negatively regulates cell proliferation. CCND1, p21, and p53 all harbor polymorphisms of hypothesized functional relevance that have been extensively studied in the context of cancer (Choi et al. 2008; Lu et al. 2008; Zhou et al. 2007). In this study, we examined whether these polymorphisms modified the degree to which the age-related FEF25–75 decline was attenuated by reduced exposure to PM with aerodynamic diameter ≤ 10 μm (PM10). |
| Databáze: | OpenAIRE |
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