title: Ambient vapor samples activate the Nrf2-ARE pathway in human bronchial epithelial BEAS-2B cells.
abstract: Ambient air pollutants have been reported to induce oxidative stress based inflammatory responses in humans and experimental animals. However, most of these reports describe the actions of the particulate phase of ambient and exhaust samples. We describe here results of studies investigating the actions of the vapor phase of ambient air samples collected in the midtown area of Los Angeles on human bronchial epithelial BEAS-2B cells using DNA microarray analysis. Among 26 genes whose expression increased fourfold or more, four genes were associated with detoxifying genes regulated by the transcription factor Nrf2. Consistent with these results, the vapor samples activate the Nrf2-ARE pathway, resulting in up-regulation of heme oxygenase-1 (HO-1), glutamate cysteine ligase modifier subunit, and cystine transporter (xCT) mRNA and proteins. No appreciable increases in pro-inflammatory genes were observed. These results suggest that ambient vapor samples activate the Nrf2-ARE pathway but not an inflammatory response. Also, treatment of the vapor samples with glutathione resulted in reduction in the Nrf2 activation and HO-1 induction, suggesting that electrophiles in vapor samples contribute to this Nrf2-dependent antioxidant or adaptive response.
authors: Environmental Biology Section, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan; Graduate School of Life and Environmental Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan.
authors: Yasuhiro
authors: Y
authors: Shinkai
authors: Syun
authors: S
authors: Nakajima
authors: Arantza
authors: A
authors: Eiguren-Fernandez
authors: Emma
authors: E
authors: Di Stefano
authors: Debra A
authors: DA
authors: Schmitz
authors: John R
authors: JR
authors: Froines
authors: Arthur K
authors: AK
authors: Cho
authors: Yoshito
authors: Y
authors: Kumagai
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D061745:Antioxidant Response Elements; D000975:Antioxidants / Q000378:metabolism; D001980:Bronchi / Q000166:cytology*; D004847:Epithelial Cells / Q000187:drug effects* / Q000378:metabolism; D005721:Glutamate-Cysteine Ligase / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051267:NF-E2-Related Factor 2 / Q000235:genetics / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D015854:Up-Regulation; D014835:Volatilization
chemical_list: D000393:Air Pollutants; D000975:Antioxidants; D051267:NF-E2-Related Factor 2; D012333:RNA, Messenger; D051547:Heme Oxygenase-1; C546365:GCLM protein, human; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione
keywords: Nrf2; ambient air sample; electrophile; microarray; vapor phase
references: Environ Health Perspect. 2003 Apr;111(4):455-60
references: 12676598
references: Inhal Toxicol. 2011 Dec;23(14):897-905
references: 22122303
references: Sci Signal. 2009 Sep 29;2(90):re7
references: 19797270
references: Chem Res Toxicol. 2002 Apr;15(4):483-9
references: 11952333
references: Toxicol Appl Pharmacol. 2009 Jun 1;237(2):232-6
references: 19341753
references: Am J Respir Cell Mol Biol. 1998 Jul;19(1):98-106
references: 9651185
references: Genes Dev. 1999 Jan 1;13(1):76-86
references: 9887101
references: Circulation. 2010 Jun 1;121(21):2331-78
references: 20458016
references: Environ Res. 2005 Sep;99(1):40-7
references: 16053926
references: Thromb Res. 2012 Mar;129(3):230-4
references: 22113148
references: Arch Biochem Biophys. 1996 Sep 1;333(1):233-42
references: 8806776
references: Mutat Res. 2010 Aug 7;690(1-2):24-39
references: 19769993
references: Scand J Work Environ Health. 2004;30 Suppl 2:80-90
references: 15487689
references: Am J Respir Crit Care Med. 2012 Jul 1;186(1):11-6
references: 22538803
references: J Toxicol Sci. 2011;36(6):843-5
references: 22129749
references: Annu Rev Pharmacol Toxicol. 2010;50:323-54
references: 20055707
references: J Biochem Biophys Methods. 1984 Dec;10(3-4):203-9
references: 6530509
references: Acc Chem Res. 2010 May 18;43(5):673-83
references: 20218676
references: Am J Physiol Lung Cell Mol Physiol. 2003 Jun;284(6):L1055-62
references: 12576300
references: Environ Res. 2010 Apr;110(3):207-12
references: 20152964
references: Environ Health Perspect. 2010 Jun;118(6):756-62
references: 20123637
references: Iran J Allergy Asthma Immunol. 2006 Jun;5(2):47-56
references: 17237576
references: Toxicol Appl Pharmacol. 2005 Sep 1;207(2 Suppl):269-75
references: 15993911
references: Genes Cells. 2011 Feb;16(2):123-40
references: 21251164
references: Environ Res. 2009 Apr;109(3):239-44
references: 19200952
references: J Environ Sci Health A Tox Hazard Subst Environ Eng. 2011;46(13):1469-81
references: 21961642
references: Biochem Pharmacol. 2010 Dec 15;80(12):1895-903
references: 20643109