Acute Decreases in Proteasome Pathway Activity after Inhalation of Fresh Diesel Exhaust or Secondary Organic Aerosol

• Published in: Environmental health perspectives Vol. 119; no. 5; pp. 658 - 663
• Main Authors: Kipen, Howard M., Gandhi, Sampada, Rich, David Q., Ohman-Strickland, Pamela, Laumbach, Robert, Fan, Zhi-Hua, Chen, Li, Laskin, Debra L., Zhang, Junfeng, Madura, Kiran
• Format: Journal Article
• Language: English
• Published: Research Triangle Park, NC National Institute of Environmental Health Sciences 01.05.2011; US Department of Health and Human Services
• Subjects: Adolescent; Adult; Aerosols; Aerosols - toxicity; Air; Air pollution; Air Pollution - adverse effects; Air pollution effects; Biodegradation; Biological and medical sciences; Diesel engines; Diesel exhaust; Diesel motor exhaust gas; Environment. Living conditions; Environmental health; Environmental pollutants toxicology; Enzymes; Erythrocytes - drug effects; Exposure; Female; Health aspects; Humans; Inflammation; Inhalation; Inhalation Exposure - adverse effects; Leukocytes - drug effects; Lung diseases; Male; Medical sciences; Oxidative stress; Ozone; Particulate matter; Proteasome Endopeptidase Complex - drug effects; Proteasome Endopeptidase Complex - metabolism; Proteolysis; Public health. Hygiene; Public health. Hygiene-occupational medicine; Risk factors; Toxicology; Vehicle Emissions - toxicity; Young Adult; United States; Human; Multicatalytic endopeptidase complex; Oxidative stress; diesel; proteasome; Secondary; SOA; Enzyme; Diesel fuel; Activity; Diesel engine; Inflammation; ubiquitin proteasome pathway; Inhalation; Peptidases; Health and environment; Decrease; UPP; Aerosols; secondary organic aerosol; Hydrolases; Air pollution; Exhaust gas; Public health
• DOI: 10.1289/ehp.1002784
• ISSN: 0091-6765; 1552-9924

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. Objectives: 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.