title: Nrf2-regulated phase II enzymes are induced by chronic ambient nanoparticle exposure in young mice with age-related impairments.
abstract: Many xenobiotic detoxifying (phase II) enzymes are induced by sublethal doses of environmental toxicants. However, these adaptive mechanisms have not been studied in response to vehicular-derived airborne nano-sized particulate matter (nPM). Because aging is associated with increased susceptibility to environmental toxicants, we also examined the expression of Nrf2-regulated phase II genes in middle-aged mice and their inducibility by chronic nPM. The nPM from vehicular traffic was collected in urban Los Angeles and reaerosolized for exposure of C57BL/6J male mice (3 and 18 months old) for 150 h over 10 weeks. Brain (cerebellum), liver, and lung were assayed by RT-PCR and/or Western blots for the expression of phase II enzymes, glutamate cysteine ligase (catalytic GCLC, and modifier GCLM subunits), NAD(P)H:quinone oxidoreductase 1 (NQO1), heme oxygenase 1 (HO-1), and relevant transcription factors, NF-E2-related factor 2 (Nrf2), c-Myc, Bach1. Chronic nPM exposure induced GCLC, GCLM, HO-1, NQO1 mRNA, and protein similarly in cerebellum, liver, and lung of young mice. Middle-aged mice had elevated basal levels, but showed impaired further induction by nPM. Similarly, Nrf2 increased with age and was induced by nPM in young but not old. c-Myc showed the same age and induction profile while the age increase in Bach1 was further induced by nPM. Chronic exposure to nanoparticles induced Nrf2-regulated detoxifying enzymes in brain (cerebellum), liver, and lung of young adult mice, indicating a systemic impact of nPM. In contrast, middle-aged mice did not respond above their elevated basal levels except for Bach1. The lack of induction of phase II enzymes in aging mice may be a model for the vulnerability of elderly to air pollution.
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA 90089, USA.
authors.forename: Hongqiao
authors.initials: H
authors.lastname: Zhang
authors.forename: Honglei
authors.initials: H
authors.lastname: Liu
authors.forename: Kelvin J A
authors.initials: KJ
authors.lastname: Davies
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Caleb E
authors.initials: CE
authors.lastname: Finch
authors.forename: Todd E
authors.initials: TE
authors.lastname: Morgan
authors.forename: Henry Jay
authors.initials: HJ
authors.lastname: Forman
mesh_terms: D000375:Aging / Q000378:metabolism*; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004798:Enzymes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000502:physiology*; D053758:Nanoparticles; D010316:Particle Size
chemical_list: D000393:Air Pollutants; D017931:DNA Primers; D004798:Enzymes; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse