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1.
Mol Pharmacol ; 98(5): 586-597, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32938721

RESUMO

This study investigated the roles of transient receptor potential (TRP) ankyrin-1 (TRPA1) and TRP vanilloid-3 (TRPV3) in regulating endoplasmic reticulum stress (ERS) and cytotoxicity in human bronchial epithelial cells (HBECs) treated with pneumotoxic wood smoke particulate matter (WSPM) and chemical agonists of each channel. Functions of TRPA1 and TRPV3 in pulmonary epithelial cells remain largely undefined. This study shows that TRPA1 activity localizes to the plasma membrane and endoplasmic reticulum (ER) of cells, whereas TRPV3 resides primarily in the ER. Additionally, treatment of cells using moderately cytotoxic concentrations of pine WSPM, carvacrol, and other TRPA1 agonists caused ERS as a function of both TRPA1 and TRPV3 activities. Specifically, ERS and cytotoxicity were attenuated by TRPA1 inhibition, whereas inhibiting TRPV3 exacerbated ERS and cytotoxicity. Interestingly, after treatment with pine WSPM, TRPA1 transcription was suppressed, whereas TRPV3 was increased. TRPV3 overexpression in HBECs conferred resistance to ERS and an attenuation of ERS-associated cell cycle arrest caused by WSPM and multiple prototypical ERS-inducing agents. Alternatively, short hairpin RNA-mediated knockdown of TRPV3, like the TRPV3 antagonist, exacerbated ERS. This study reveals previously undocumented roles for TRPA1 in promoting pathologic ERS and cytotoxicity elicited by pneumotoxic WSPM and TRPA1 agonists, and a unique role for TRPV3 in fettering pathologic facets of the integrated ERS response. SIGNIFICANCE STATEMENT: These findings provide new insights into how wood smoke particulate matter and other transient receptor potential ankyrin-1 (TRPA1) and transient receptor potential vanilloid-3 (TRPV3) agonists can affect human bronchial epithelial cells and highlight novel physiological and pathophysiological roles for TRPA1 and TRPV3 in these cells.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Pulmão/efeitos dos fármacos , Material Particulado/administração & dosagem , Fumaça/efeitos adversos , Canal de Cátion TRPA1/metabolismo , Canais de Cátion TRPV/metabolismo , Linhagem Celular , Cimenos/efeitos adversos , Retículo Endoplasmático/efeitos dos fármacos , Retículo Endoplasmático/metabolismo , Células Epiteliais/metabolismo , Células HEK293 , Humanos , Pulmão/metabolismo , Pinus/efeitos adversos , Canais de Potencial de Receptor Transitório/metabolismo , Madeira/efeitos adversos
2.
Chem Res Toxicol ; 32(2): 219-221, 2019 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-30721037

RESUMO

Air pollutants from burning wood and biomass pose serious human health risks. Recent discoveries link the chemistry of smoke emissions with biochemical sensors and biological effect mediators. Strategic thinking of complex underlying factors is needed to protect people from harm.


Assuntos
Medição de Risco , Fumaça/análise , Madeira/química , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Biomassa , Humanos , Pneumopatias/etiologia , Material Particulado/análise , Material Particulado/toxicidade
3.
Toxicol Sci ; 174(2): 278-290, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-31944254

RESUMO

Mucus hypersecretion is a pathological feature of acute inflammatory and chronic obstructive pulmonary diseases. Exposure to air pollutants can be a cause of pathological mucus overproduction, but mechanisms by which different forms of air pollutants elicit this response are not fully understood. In this study, particulate matter (PM) generated from burning pine wood and other types of biomass was used to determine mechanisms by which these forms of PM stimulate mucin gene expression and secretion by primary human bronchial epithelial cells (HBECs). Biomass PM < 2.5 µm generated from pine wood and several other fuels stimulated the expression and secretion of the gel-forming glycoprotein MUC5AC by HBECs. Muc5ac gene induction was also observed in mouse airways following subacute oropharyngeal delivery of pine wood smoke PM. In HBECs, MUC5AC was also induced by the transient receptor potential ankyrin-1 (TRPA1) agonists' coniferaldehyde, a component of pine smoke PM, and allyl isothiocyanate, and was attenuated by a TRPA1 antagonist. Additionally, inhibition of epidermal growth factor receptor (EGFR/ErbB1) and the EGFR signaling partners p38 MAPK and GSK3ß also prevented MUC5AC overexpression. Collectively, our results suggest that activation of TRPA1 and EGFR, paired with alterations to p38 MAPK and GSK3ß activity, plays a major role in MUC5AC overproduction by bronchial epithelial cells exposed to biomass smoke PM. These results reveal specific processes for how biomass smoke PM may impact the human respiratory system and highlight potential avenues for therapeutic manipulation of lung diseases that are affected by air pollutants.


Assuntos
Brônquios/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Mucina-5AC/metabolismo , Fumaça/efeitos adversos , Canal de Cátion TRPA1/metabolismo , Animais , Brônquios/metabolismo , Células Cultivadas , Células Epiteliais/metabolismo , Receptores ErbB/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Exposição por Inalação , Camundongos Endogâmicos C57BL , Mucina-5AC/genética , Transdução de Sinais , Regulação para Cima , Madeira , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
4.
Sci Total Environ ; 749: 141273, 2020 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-32836114

RESUMO

The specific source of high burdens of selenium (Se) and mercury (Hg) in several bird species at Great Salt Lake (GSL) remain unknown. Frequent co-located water and brine shrimp samples were collected during 2016 through 2017 to identify potential correlations of element concentrations among brines and brine shrimp, a keystone species in the GSL. Like many aquatic systems, GSL is characterized by elevated methylmercury (MeHg) in deep waters. However, in contrast to thermally-stratified aquatic systems, biota in the salinity-stratified GSL do not reside in its deep waters, obscuring the presumed relationship between elevated MeHg in biota and in the deep brine. Brine shrimp and water column (shallow and deep, filtered and unfiltered) samples were collected from six sites spanning the South Arm of GSL approximately every other month. Mercury concentrations in brine shrimp (on average 89% of which is MeHg) were correlated only with total mercury in surface filtered water, and displayed little spatial variability, but consistent seasonal trends across the two sampled years. In contrast to Hg, temporal correspondence was observed between Se concentrations in brine shrimp and those in all water samples regardless of filtering and depth, with maxima and minima at higher-than-seasonal frequency. The data suggest a spatially diffuse source of bioavailable mercury to the shallow brine that responds to seasonal influences, for which the underlying deep brine, surficial sediments, and overlying atmosphere were evaluated in terms of potential temporal correspondence to shallow brine and brine shrimp Hg concentrations, as well as potential to mix across the extent of the shallow brine. Bioaccumulation factors were at the low end of those reported for marine systems, and decreased at higher trace element concentrations in water.


Assuntos
Mercúrio , Compostos de Metilmercúrio , Selênio , Poluentes Químicos da Água , Animais , Artemia , Monitoramento Ambiental , Lagos , Mercúrio/análise , Selênio/análise , Utah , Água , Poluentes Químicos da Água/análise
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