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Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity Cassandra Deering-Rice, Nam Nguyen, Zhenyu Lu, James Cox, Darien Shapiro, Erin G. Romero, Virginia K. Mitchell, Katherine L. Burrell, John M. Veranth, and Christopher A Reilly Chem. Res. Toxicol., Just Accepted Manuscript • DOI: 10.1021/acs.chemrestox.7b00336 • Publication Date (Web): 16 Apr 2018 Downloaded from http://pubs.acs.org on April 16, 2018
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Chemical Research in Toxicology
Activation of TRPV3 by Wood Smoke Particles and Roles in Pneumotoxicity Cassandra E. Deering-Rice†, Nam Nguyen1, Zhenyu Lu†, James E. Cox‡, Darien Shapiro†, Erin G. Romero†, Virginia K. Mitchell†, Katherine L. Burrell†, John M. Veranth†, and Christopher A. Reilly†* †
Department of Pharmacology and Toxicology, Center for Human Toxicology, 30 S. 2000 E., Room 201 Skaggs Hall, University of Utah, Salt Lake City, UT 84112. ‡
Department of Biochemistry, Emma Eccles Jones Medical Research Building Room: A306, 15 N Medical Drive E., University of Utah, Salt Lake City, UT 84112. Cassandra E. Deering-Rice –
[email protected] Zhenyu Lu –
[email protected] Nam Nguyen -
[email protected] James E. Cox –
[email protected] Darien Shapiro –
[email protected] Erin G. Romero –
[email protected] Virginia K. Mitchell –
[email protected] Katherine L. Burrell –
[email protected] John M. Veranth –
[email protected] Christopher A. Reilly –
[email protected] *
Corresponding author: Dr. Christopher A. Reilly, Ph.D. University of Utah Department of Pharmacology and Toxicology 30 South 2000 East, 201 Skaggs Hall Salt Lake City, UT 84112 Phone: (801) 581-5236; FAX: (801) 585-5111 Email:
[email protected] Key words: Transient Receptor Vanilloid 3 (TRPV3), wood smoke, lung epithelial cells
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Chemical Research in Toxicology
Abstract: (250 words) Wood/biomass smoke particulate materials (WBSPM) are pneumotoxic, but mechanisms by which these materials affect lung cells are not fully understood. We previously identified transient receptor potential (TRP) ankyrin-1 as a sensor for electrophiles in WBSPM and hypothesized that other TRP channels expressed by lung cells might also be activated by WBSPM, contributing to pneumotoxicity. Screening TRP channel activation by WBSPM using calcium flux assays revealed TRPV3 activation by materials obtained from burning multiple types of wood under fixed conditions. TRPV3 activation by WBSPM was dependent on the chemical composition and the pattern of activation and chemical components of PM agonists was different from that of TRPA1. Chemical analysis of particle constituents by gas chromatography-mass spectrometry and principal component analysis, indicated enrichment of cresol, ethyl-phenol, and xylenol analogues, plus several other chemicals among the most potent samples. 2,3-, 2,4-, 2,5-, 2,6-, 3,4-, 3,5-xylenol, 2-, 3-, 4-ethyphenol, 2-methoxy-4-methylphenol, and 5,8-dihydronaphthol were TRPV3 agonists exhibiting preferential activation versus TRPA1, M8, V1, and V4. The concentration of 2,3- and 3,4-xylenol in the most potent samples of pine and mesquite smoke PM (
