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

Autor: Debra L. Laskin, Kiran Madura, Junfeng Zhang, Zhihua Fan, Li Chen, David Q. Rich, Howard M. Kipen, Pamela Ohman-Strickland, Robert Laumbach, Sampada K. Gandhi
Rok vydání: 2011
Předmět:
Zdroj: Environmental Health Perspectives
ISSN: 1552-9924
0091-6765
DOI: 10.1289/ehp.1002784
Popis: 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.
Databáze: OpenAIRE