Ultrafine Particles and Mitochondrial Dysfunction

Central Washington University, Ellensburg WA

Investigators

Abstract

DESCRIPTION (provided by applicant): Atmospheric ultrafine particulates (UFPs, mass median aerodynamic diameter < 0.1 mu m) emitted from combustion processes and newly emerging nanotechnologies have recently been recognized as a significant global health hazard. Inhalation of these particles may lead to disruption of mitochondrial cristae and increased levels of reactive oxygen species (ROS) in lung epithelial cells. The respiratory and cardiovascular systems seem particularly vulnerable to the toxic effects of UFPs through a combination of the particles' characteristically large surface area and the presence of surface transition metals and polycyclic aromatic hydrocarbons (PAHs). Nevertheless, the surface chemistry of UFPs remains virtually unexplored and has not been correlated with possible toxicological mechanisms. The long-term objective of the present study is to identify the main contributors and processes that initiate the physiological detrimental effects of UFPs. The primary focus is on establishing that surface compounds that contribute to the production of ROS, principally iron and PAHs, can cause direct mitochondrial damage. UFPs will be collected in urban and rural areas of Washington State and analyzed for surface iron speciation and PAHs using x-ray photoelectron spectroscopy (XPS), time of flight secondary ion mass spectrometry (TOF-SIMS), and spectrophotometry. Simultaneously, their toxicological effects will be tested in vitro on beef heart mitochondria, with particular interest on whether the initial mechanisms of mitochondrial dysfunction are lipid peroxidation or ROS production and electron transport inhibition. Findings from this multidisciplinary project involving the collaborative expertise of atmospheric, surface, and biochemists will bridge critical gaps tying UFP characteristics to their toxicological mechanisms in cellular metabolism and contribute to current understanding of health effects of airborne particulate matter.