title: Acute decreases in proteasome pathway activity after inhalation of fresh diesel exhaust or secondary organic aerosol.
abstract: BACKGROUND
  Epidemiologic studies consistently demonstrate an association between acute cardiopulmonary events and changes in air pollution; however, the mechanisms that underlie these associations are not completely understood. Oxidative stress and inflammation have been suggested to play a role in human responses to air pollution. The proteasome is an intracellular protein degradation system linked to both of these processes and may help mediate air pollution effects.
  
  
  OBJECTIVE
  In these studies, we determined whether acute experimental exposure to two different aerosols altered white blood cell (WBC) or red blood cell (RBC) proteasome activity in human subjects. One aerosol was fresh diesel exhaust (DE), and the other freshly generated secondary organic aerosol (SOA).
  
  
  METHODS
  Thirty-eight healthy subjects underwent 2-hr resting inhalation exposures to DE and separate exposures to clean air (CA); 26 subjects were exposed to DE, CA, and SOA. CA responses were subtracted from DE or SOA responses, and mixed linear models with F-tests were used to test the effect of exposure to each aerosol on WBC and RBC proteasome activity.
  
  
  RESULTS
  WBC proteasome activity was reduced 8% (p = 0.04) after exposure to either DE or SOA and decreased by 11.5% (p = 0.03) when SOA was analyzed alone. RBCs showed similar 8-10% declines in proteasome activity (p = 0.05 for DE alone).
  
  
  CONCLUSIONS
  Air pollution produces oxidative stress and inflammation in many experimental models, including humans. Two experimental aerosols caused rapid declines in proteasome activity in peripheral blood cells, supporting a key role for the proteasome in acute human responses to air pollution.
authors.affiliation: Clinical Research and Occupational Medicine Division, Environmental and Occupational Health Sciences Institute, Piscataway, New Jersey 08854, USA. kipen@eohsi.rutgers.edu
authors.forename: Howard M
authors.initials: HM
authors.lastname: Kipen
authors.forename: Sampada
authors.initials: S
authors.lastname: Gandhi
authors.forename: David Q
authors.initials: DQ
authors.lastname: Rich
authors.forename: Pamela
authors.initials: P
authors.lastname: Ohman-Strickland
authors.forename: Robert
authors.initials: R
authors.lastname: Laumbach
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Fan
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.forename: Debra L
authors.initials: DL
authors.lastname: Laskin
authors.forename: Junfeng
authors.initials: J
authors.lastname: Zhang
authors.forename: Kiran
authors.initials: K
authors.lastname: Madura
mesh_terms: D000293:Adolescent; D000328:Adult; D000336:Aerosols / Q000633:toxicity*; D000397:Air Pollution / Q000009:adverse effects*; D004912:Erythrocytes / Q000187:drug effects; D005260:Female; D006801:Humans; D019570:Inhalation Exposure / Q000009:adverse effects; D007962:Leukocytes / Q000187:drug effects; D008297:Male; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism*; D001335:Vehicle Emissions / Q000633:toxicity*; D055815:Young Adult
chemical_list: D000336:Aerosols; D001335:Vehicle Emissions; D046988:Proteasome Endopeptidase Complex