Proteome-wide effects of naphthalene-derived secondary organic aerosol in BEAS-2B cells are caused by short-lived unsaturated carbonyls

Abstract

Exposure to air pollution causes adverse health outcomes, but the toxicity mechanisms remain unclear. Here, we investigated the dynamic toxicities of naphthalene-derived secondary organic aerosol (NSOA) in a human bronchial epithelial cell line (BEAS-2B) and identified the chemical components responsible for toxicities. The chemical composition of NSOA was found to vary with six simulated atmospheric aging conditions (C1–C6), as characterized by high-resolution mass spectrometry and ion mobility mass spectrometry. Global proteome profiling reveals dynamic evolution in toxicity: Stronger proteome-wide impacts were detected in fresh NSOA, but the effects declined along with atmospheric aging. While Nrf2-regulated proteins (e.g., NQO1) were significantly up-regulated, the majority (78 to 97%) of proteins from inflammation and other pathways were down-regulated by NSOA exposure (e.g., Rho GTPases). This pattern is distinct from the reactive oxygen species (ROS)-mediated toxicity pathway, and an alternative cysteine reaction pathway was revealed by the decreased abundance of proteins (e.g., MT1X) prone to posttranslational thiol modification. This pathway was further validated by observing decreased Nrf2 response in reporter cells, after preincubating NSOA with cysteine. Ethynyl-naphthalene probe was employed to confirm the alkylation of cellular proteome thiols on the proteome-wide level by fresh NSOA via in-gel fluorescence imaging. Nontarget analysis identified several unsaturated carbonyls, including naphthoquinones and hydroxylated naphthoquinones, as the toxic components responsible for cysteine reactivity. Our study provides insights into the dynamic toxicities of NSOA during atmospheric aging and identifies short-lived unsaturated carbonyls as the predominant toxic components at the posttranslational level.

Effect of Atmospheric Aging on Soot Particle Toxicity in Lung Cell Models at the Air–Liquid Interface: Differential Toxicological Impacts of Biogenic and Anthropogenic Secondary Organic Aerosols (SOAs)

“…The present study shows that compared with had an adverse outcome on cell viability, oxidative stress, genotoxicity, and inflammation consistent with previous studies ( Chowdhury et al. 2018 , 2019 ; Han et al. 2020 ) and, in addition, induced a pro-angiogenic potential in endothelial cells.…”

“…2018 ). However, it has to be noted that this increased toxicity reflected specific oxidation stages and could change with oxidation mechanism given that studies have also shown a declined toxicity during aging for naphthalene ( Han et al. 2020 ) or hydrocarbons ( Jiang and Jang 2018 ).…”

“…A recent in vitro proteome-wide study by Han et al. ( 2020 ) pointed out the importance of short-lived unsaturated carbonyls in aged naphthalene as the main toxic components at the posttranslational level. Furthermore, the oxidation of furan-containing compounds favored the formation of epoxides, which are associated with enhanced harmful cellular effects ( Peterson 2013 ; Tǎbǎran et al.…”

Secondary organic aerosol formation from monocyclic aromatic hydrocarbons: insights from laboratory studies

“…165 Quinones present in SOA are suggested as toxic constituents to humans because they are reactive to cysteine and have high DTT activity. 166 SOA generated from monocyclic aromatic hydrocarbons contain trace amount of quinones or even no quinones. However, Jiang et al and Tuet et al also highlighted the importance of SOA from monocyclic aromatic hydrocarbons on health effects due to their high DTT activity.…”

Quantitative Chemical Proteomics Reveals Interspecies Variations on Binding Schemes of L-FABP with Perfluorooctanesulfonate

“…Probe-based chemical proteomics, e.g. , activity-based protein profiling (ABPP), has made important progress in recent years to identify protein targets of small molecules on a proteome-wide level. − However, the application of probe-based chemical proteomics to quantitative chemical–protein interactions is limited by its intrinsic insensitivity to binding affinity. Methods for probe-free chemical proteomics have been recently developed based on protein thermal stability, conformation changes, or protease accessibility from our group and others. − Probe-free chemical proteomics is time-effective to evaluate many chemicals of interests, without the need for laborious chemical probe synthesis.…”