title: Brain suppression of AP-1 by inhaled diesel exhaust and reversal by cerium oxide nanoparticles.
abstract: One of the uses of cerium oxide nanoparticles (nanoceria, CeO2) is as a diesel fuel additive to improve fuel efficiency. Gene/environment interactions are important determinants in the etiology of age-related disorders. Thus, it is possible that individuals on high-fat diet and genetic predisposition to vascular disease may be more vulnerable to the adverse health effects of particle exposure. The aim of this pilot study was to test the hypothesis that inhalation of diesel exhaust (DE) or diesel exhaust-containing cerium oxide nanoparticles (DCeE) induces stress in the brain of a susceptible animal model. Atherosclerotic prone, apolipoprotein E knockout (ApoE(-/-)) mice fed a high-fat diet, were exposed by inhalation to purified air (control), DE or DCeE. The stress-responsive transcription factor, activator protein-1 (AP-1), was significantly decreased in the cortical and subcortical fraction of the brain after DE exposure. The addition of nanoceria to the diesel fuel reversed this effect. The activation of another stress-related transcription factor (NF-κB) was not inhibited. AP-1 is composed of complexes of the Jun and/or Fos family of proteins. Exposure to DCeE caused c-Jun activation and this may be a mechanism by which addition of nanoceria to the fuel reversed the effect of DE exposure on AP-1 activation. This pilot study demonstrates that exposure to DE does impact the brain and addition of nanoceria may be protective. However, more extensive studies are necessary to determine how DE induced reduction of AP-1 activity and compensation by nanoceria impacts normal function of the brain.
authors.affiliation: Department of Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences , Pomona, CA , USA and.
authors.forename: Shyang
authors.initials: S
authors.lastname: Lung
authors.forename: Flemming R
authors.initials: FR
authors.lastname: Cassee
authors.forename: Ilse
authors.initials: I
authors.lastname: Gosens
authors.forename: Arezoo
authors.initials: A
authors.lastname: Campbell
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control; D015153:Blotting, Western; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002563:Cerium / Q000737:chemistry / Q000494:pharmacology*; D059305:Diet, High-Fat / Q000009:adverse effects; D024202:Electrophoretic Mobility Shift Assay; D005742:Gasoline / Q000032:analysis; D019570:Inhalation Exposure / Q000009:adverse effects*; D018345:Mice, Knockout; D053758:Nanoparticles / Q000737:chemistry*; D010865:Pilot Projects; D020011:Protective Agents / Q000737:chemistry / Q000494:pharmacology*; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors*; D001335:Vehicle Emissions / Q000633:toxicity*
chemical_list: D001057:Apolipoproteins E; D005742:Gasoline; D020011:Protective Agents; D018808:Transcription Factor AP-1; D001335:Vehicle Emissions; D002563:Cerium; C030583:ceric oxide
keywords: c-Jun; nanoceria; stress; transcription factors