title: Exposure to Concentrated Ambient PM2.5 Shortens Lifespan and Induces Inflammation-Associated Signaling and Oxidative Stress in Drosophila.
abstract: Exposure to ambient PM 2.5 is associated with human premature mortality. However, it has not yet been toxicologically replicated, likely due to the lack of suitable animal models. Drosophila is frequently used in longevity research due to many incomparable merits. The present study aims to validate Drosophila models for PM 2.5 toxicity study through characterizing their biological responses to exposure to concentrated ambient PM 2.5 (CAP). The survivorship curve demonstrated that exposure to CAP markedly reduced lifespan of Drosophila. This antilongevity effect of CAP exposure was observed in both male and female Drosophila, and by comparison, the male was more sensitive [50% survivals: 20 and 48 days, CAP- and filtered air (FA)-exposed males, respectively; 21 and 40 days, CAP- and FA-exposed females, respectively]. Similar to its putative pathogenesis in humans, CAP exposure-induced premature mortality in Drosophila was also coincided with activation of pro-inflammatory signaling pathways including Jak, Jnk, and Nf-κb and increased systemic oxidative stress. Furthermore, like in humans and mammals, exposure to CAP significantly increased whole-body and circulating glucose levels and increased mRNA expression of Ilp2 and Ilp5 , indicating that CAP exposure induces dysregulated insulin signaling in Drosophila. Similar to effects on humans exposure to CAP leads to premature mortality likely through induction of inflammation-associated signaling, oxidative stress, and metabolic abnormality in Drosophila, strongly supporting that it can be a useful model organism for PM 2.5 toxicity study.
authors.affiliation: Department of Occupational and Environmental Health, School of Public Health, Nantong University, Nantong 226019, China.|Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Xiaoke
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland 21201.|Department of Environmental Health School of Public Health, Fudan University, Shanghai 200032, China.
authors.forename: Minjie
authors.initials: M
authors.lastname: Chen
authors.affiliation: Department of Nutrition and Food hygiene School of Public Health, Nantong University, Nantong 226019, China.
authors.forename: Mianhua
authors.initials: M
authors.lastname: Zhong
authors.affiliation: Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Ziying
authors.initials: Z
authors.lastname: Hu
authors.affiliation: Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland 21201.|Center for Vascular and Inflammatory Diseases and the Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Lianglin
authors.initials: L
authors.lastname: Qiu
authors.affiliation: Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Sanjay
authors.initials: S
authors.lastname: Rajagopalan
authors.affiliation: Center for Vascular and Inflammatory Diseases and the Department of Pathology, University of Maryland School of Medicine, Baltimore, Maryland 21201.
authors.forename: Nancy G
authors.initials: NG
authors.lastname: Fossett
authors.affiliation: Department of Environmental Medicine School of Medicine, New York University Tuxedo, New York, New York 10987.
authors.forename: Lung-Chi
authors.initials: LC
authors.lastname: Chen
authors.affiliation: Department of Medicine Cardiology Division, University of Maryland School of Medicine, Baltimore, Maryland 21201.|Department of Environmental Health School of Public Health, Fudan University, Shanghai 200032, China.
authors.forename: Zhekang
authors.initials: Z
authors.lastname: Ying
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D030801:Animals, Genetically Modified; D001273:Atmosphere Exposure Chambers; D029721:Drosophila Proteins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000187:drug effects* / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D004351:Drug Resistance; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D017930:Genes, Reporter / Q000187:drug effects; D005947:Glucose / Q000819:agonists / Q000378:metabolism; D006458:Hemolymph / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D007333:Insulin Resistance; D061385:Insulins / Q000819:agonists / Q000235:genetics / Q000378:metabolism; D008136:Longevity / Q000187:drug effects; D020935:MAP Kinase Signaling System / Q000187:drug effects*; D008297:Male; D009479:Neuropeptides; D018384:Oxidative Stress / Q000187:drug effects*; D052638:Particulate Matter / Q000633:toxicity*; D012727:Sex Characteristics; D016019:Survival Analysis; D036401:Toxicity Tests, Chronic / Q000379:methods*
chemical_list: D000393:Air Pollutants; D029721:Drosophila Proteins; C544178:ILP2 protein, Drosophila; C570846:Ilp5 protein, Drosophila; D061385:Insulins; D009479:Neuropeptides; D052638:Particulate Matter; D005947:Glucose
keywords: PM2.5; drosophila; inflammation-associated signaling; lifespan; oxidative stress.