Linking Cell Health and Reactive Oxygen Species from Secondary Organic Aerosols Exposure

Abstract

Oxidative stress is a possible mechanism by which ambient fine particulate matter (PM) exerts adverse biological effects. While multiple biological effects and reactive oxygen species (ROS) production have been observed upon PM exposure, whether the biological effects are ROS-mediated remains unclear. Secondary organic aerosols (SOA) constitute a major fraction of fine PM and can contribute substantially to its toxicity. In this work, we measured three types of cell responses (mitochondrial membrane potential (MMP), caspase 3/7 activity, and ROS) and investigated their associations upon exposure to SOA formed from anthropogenic (naphthalene) and biogenic (α-pinene) precursors. MMP and caspase 3/7 activity (an early indicator of apoptosis) are key indicators of cell health, and changes of them could occur downstream of ROS-mediated pathways. We observed a significant increase in caspase 3/7 activity after SOA exposure, suggesting that apoptosis is an important pathway of cell death induced by SOA. We further found strong associations between a decrease in MMP and increase in caspase 3/7 activity with an increase in cellular ROS level. These results suggest that cell health is largely dependent on the cellular ROS level, highlighting oxidative stress as a key mechanism for biological effects from SOA exposure. Linear regression analyses reveal greater changes of the three cellular responses with increasing carbon oxidation state (OSc) of SOA, suggesting that SOA are more toxic when they are more oxidized. Overall, our work provides critical insights into the associations between cell health and ROS level upon SOA exposure and proposes that OSc could be a suitable proxy to assess the overall SOA toxicity.

Oxidized and Unsaturated: Key Organic Aerosol Traits Associated with Cellular Reactive Oxygen Species Production in the Southeastern United States

“…LO-OOA is fresh SOA largely formed from oxidation of organic gases . MO-OOA is highly oxidized and can be formed from multiple sources and pathways, including photochemical aging of fresh SOA, aqueous processes, chemical processing during long-range transport, partitioning of highly oxygenated molecules (HOMs), and entrainment of aged SOA from the residual layer. ,− Although the strong association between cellular ROS and MO-OOA does not necessarily establish causation, previous laboratory work has reported that aged SOA induces higher cellular ROS production compared to fresh SOA, ,, whereas only SOA formed from a single gaseous precursor was investigated in these laboratory studies. The impact of atmospheric aging processes on the cellular ROS production of ambient PM 2.5 has not been well explored.…”

“…This cell line has been used for measuring cellular ROS production upon PM exposure in a number of prior studies. 11,15,[30][31][32]36,51 PM 2.5 filters were extracted following the established protocol where the filters were submerged in RPMI-1640 media and sonicated for 30 min. 11 Note that some studies suggest that antioxidants and ligands in the lung fluid may consume or complex with PM components.…”

“…Alveolar macrophages are the first line of defense against inhaled environmental contaminants. This cell line has been used for measuring cellular ROS production upon PM exposure in a number of prior studies. ,,− ,, …”

“…A few laboratory studies have investigated the cellular toxicity of SOA formed from a single gaseous precursor under well-controlled conditions. − These studies show that the oxidative properties of SOA largely depend on SOA precursors and reaction conditions. SOA formed from aromatic-ring-containing precursors is found to induce higher levels of cellular ROS production and inflammatory response. , Laboratory investigations also suggest that atmospheric aging processes can enhance SOA cellular toxicity. ,,, Consistent with these cellular studies, increasing aerosol toxicity with atmospheric aging has also been noted utilizing acellular assays, such as dithiothreitol assay. , Field investigations have found that some species such as quinone-type compounds and organic peroxides in OA significantly contribute to cellular ROS production. ,− However, detailed chemical characterization of ambient PM is still needed to determine the types and chemical features of OA that drive cellular ROS production.…”

Chemical Fate of Oils on Indoor Surfaces: Ozonolysis and Peroxidation

“…It is well-known that both ozonolysis ,, and autoxidation reactions of lipid aerosol impact air quality and climate. , In particular, organic peroxide formation in aerosol has drawn substantial research attention recently. Not only may it affect the oxidizing ability of the atmosphere through decomposition, − but also ROS exposure through inhalation of particulate matter is often linked to aerosol toxicity. − As well, the presence of lipid-base peroxides in the ambient air could also contribute to the germicidal power of the atmosphere …”