DOI: 10.5061/dryad.jd79404
title: Data from: Early mechanistic events induced by low molecular weight polycyclic aromatic hydrocarbons in mouse lung epithelial cells: a role for eicosanoid signaling

description: Low molecular weight polycyclic aromatic hydrocarbons (LMW PAHs;
 &lt;206.3 g/mol) are under regulated environmental contaminants (e.g.,
 secondhand smoke) that lead to gap junction dysregulation, p38 MAPK
 activation, and increased mRNA production of inflammatory mediators, such
 as cytokines and cyclooxygenase (COX2), in lung epithelial cells. However,
 the early mechanisms involving lipid signaling through the arachidonic
 acid pathway and subsequent eicosanoid production leading to these
 downstream events are not known. Common human exposures are to mixtures of
 LMW PAH’s, thus C10 cells (a mouse lung epithelial cell line) were exposed
 to a representative binary PAH mixture, 1-methylanthracene (1-MeA) and
 fluoranthene (Flthn), for 30 min – 24 h with and without p38 and cytosolic
 phospholipase A2 (cPLA2) inhibitors. cPLA2 inhibition reversed PAH-induced
 phospho-p38 MAPK activation and gap junction dysregulation at 30 min. A
 significant biphasic increase of cPLA2 protein was observed at 30 min, 2,
 & 4 h, as well as COX2 protein at 2 & 8 h. Untargeted
 metabolomics demonstrated a similar trend with significantly changing
 metabolites at 30 min & 4 h of exposure relative to 1 h; a
 “cPLA2-like” subset of metabolites within the biphasic response were
 predominately phospholipids. argeted metabolomics showed several
 eicosanoids (e.g., prostaglandin D2 (PGD2), PGE2α) were significantly
 increased at 4, 8, and 12 h following exposure to the binary PAH mixture
 and this effect was p38-dependent. Lastly, PAH metabolism was not observed
 until after 8 h. These results indicate an early lipid signaling mechanism
 of PAH toxicity in lung epithelial cells due to parent PAH compounds.
description: Supplementary Table
 S3Supplementary Table S3:
 Temporally significant metabolites from DMSO treatment as determined by
 t-test, p&lt;0.05. These tables include all metabolites that were
 significantly changing from DMSO control treatment between A) 0.5 – 1 h
 (72 metabolites), B) 0.5 – 4 h (76 metabolites), and C) 1 - 4 h (25
 metabolites). Metabolites were included in this table if annotated with
 either KEGGID or HMDBID. Tables include compound name, KEGGID (if
 applicable), HMDBID (if applicable), and p-value from t-test (methods
 described above).12-20-18-AKB-Suppl_Table
 S3.xlsxSupplementary Table
 S4Supplementary Table S4:
 Temporally significant metabolites from the binary PAH mixture treatment
 as determined by t-test, p&lt;0.05. These tables include all metabolites
 that were significantly changing from binary PAH mixture (40 M; 1:1 ratio
 of 1-methylanthracene and fluoranthene) treatment between A) 0.5 – 1 h
 (395 metabolites), B) 0.5 – 4 h (355 metabolites), and C) 1 - 4 h (284
 metabolites). Metabolites were included in this table if annotated with
 either KEGGID or HMDBID. Tables include compound name, KEGGID (if
 applicable), HMDBID (if applicable), and p-value from t-test (methods
 described above).12-20-18-AKB-Suppl_Table
 S4.xlsxSupplementary Table
 S5Supplementary Table S5:
 Metabolites detected from untargeted analysis via LC/MS at 0.5, 1, and 4 h
 in C10 cells. These tables include all metabolites detected in C10 cells
 at A) 0.5, B) 1, and C) 4 h. There are 3291 metabolites in A, 3561
 metabolites in B, and 3474 metabolites in C. Metabolites were detected via
 LC/MS using methods described above. Each table includes compound
 name/formula, KEGGID (if applicable), HMDB-ID (if applicable),
 t-statistic, p-value, adjusted p-value, fold change, and fold change
 geometric mean. Statistical values were determined based on methods
 described above.1-18-19-AKB-Supple_Table
 S5.xlsxRaw data for the
 targeted lipidomics studyThis data is at
 metabolomics workbench. Accession number ST001124.
 http://www.metabolomicsworkbench.orgRaw data for the
 untargeted metabolomics studyThis data is at the
 metabolomics workbench. Accession number ST001094.
 http://www.metabolomicsworkbench.org