Organic chemicals from diesel exhaust particles affects intracellular calcium, inflammation and β-adrenoceptors in endothelial cells

Brinchmann, Bendik Christian; Ferrec, Eric Le; Podechard, Normand; Lagadic‐Gossmann, Dominique; Holme, Jørn A.; Øvrevik, Johan

doi:10.1016/j.toxlet.2018.11.009

Cited by 12 publications

(10 citation statements)

References 60 publications

(102 reference statements)

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“…In line with this, we have observed that the lipophilic DEP-EOM tested in the current study also induces increased expression of pro-inflammatory genes in HMEC-1, as well as primary human endothelial cells through AhR-dependent mechanisms [ 16 ]. Recent results from our lab suggest that these pro-inflammatory responses can at least partly be attributed to the Ca 2+ signalling, but also that enhanced calcium signalling may occur without a corresponding enhancement of the inflammatory reactions [ 77 ]. Thus, calcium signaling most likely affect regulation of pro-inflammatory genes by acting in concert with other signalling pathways.…”

Section: Discussionmentioning

confidence: 99%

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Brinchmann

Ferrec

Podechard

et al. 2018

IJMS

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Exposure to diesel exhaust particles (DEPs) affects endothelial function and may contribute to the development of atherosclerosis and vasomotor dysfunction. As intracellular calcium concentration [Ca2+]i is considered important in myoendothelial signalling, we explored the effects of extractable organic matter from DEPs (DEP-EOM) on [Ca2+]i and membrane microstructure in endothelial cells. DEP-EOM of increasing polarity was obtained by pressurized sequential extraction of DEPs with n-hexane (n-Hex-EOM), dichloromethane (DCM-EOM), methanol, and water. Chemical analysis revealed that the majority of organic matter was extracted by the n-Hex- and DCM-EOM, with polycyclic aromatic hydrocarbons primarily occurring in n-Hex-EOM. The concentration of calcium was measured in human microvascular endothelial cells (HMEC-1) using micro-spectrofluorometry. The lipophilic n-Hex-EOM and DCM-EOM, but not the more polar methanol- and water-soluble extracts, induced rapid [Ca2+]i increases in HMEC-1. n-Hex-EOM triggered [Ca2+]i increase from intracellular stores, followed by extracellular calcium influx consistent with store operated calcium entry (SOCE). By contrast, the less lipophilic DCM-EOM triggered [Ca2+]i increase via extracellular influx alone, resembling receptor operated calcium entry (ROCE). Both extracts increased [Ca2+]i via aryl hydrocarbon receptor (AhR) non-genomic signalling, verified by pharmacological inhibition and RNA-interference. Moreover, DCM-EOM appeared to induce an AhR-dependent reduction in the global plasma membrane order, as visualized by confocal fluorescence microscopy. DCM-EOM-triggered [Ca2+]i increase and membrane alterations were attenuated by the membrane stabilizing lipid cholesterol. In conclusion, lipophilic constituents of DEPs extracted by n-hexane and DCM seem to induce rapid AhR-dependent [Ca2+]i increase in HMEC-1 endothelial cells, possibly involving both ROCE and SOCE-mediated mechanisms. The semi-lipophilic fraction extracted by DCM also caused an AhR-dependent reduction in global membrane order, which appeared to be connected to the [Ca2+]i increase.

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Section: Discussionmentioning

confidence: 99%

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Brinchmann

Ferrec

Podechard

et al. 2018

IJMS

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“…PARs are central for regulating vascular function, and activation may promote conversion of endothelial cells into a pro-inflammatory phenotype in conditions associated with endothelial dysfunction [194]. Recently it was reported that both induction of inflammation-associated genes and [Ca 2+ ] i , partly depended on PAR-2 in endothelial cells exposed to lipophilic organic chemicals from DEP [48, 195].…”

Section: The Role Of Organic Chemicals and Pah In Mediating Cvdmentioning

confidence: 99%

“…This differs distinctly from B[ a ]P-induced Ca 2+ -signaling through β2ADR [112], and suggest that PAHs may affect [Ca 2+ ] i -regulation in endothelial cell through different mechanisms. Notably, studies on effect of lipophilic organic chemicals extracted from DEP, suggest that their induction of [Ca 2+ ] i could involve both AhR- and β2ADR-dependent responses [119, 195].…”

Section: The Role Of Organic Chemicals and Pah In Mediating Cvdmentioning

confidence: 99%

Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles

et al. 2019

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Air pollution is the most important environmental risk factor for disease and premature death, and exposure to combustion particles from vehicles is a major contributor. Human epidemiological studies combined with experimental studies strongly suggest that exposure to combustion particles may enhance the risk of cardiovascular disease (CVD), including atherosclerosis, hypertension, thrombosis and myocardial infarction. In this review we hypothesize that adhered organic chemicals like polycyclic aromatic hydrocarbons (PAHs), contribute to development or exacerbation of CVD from combustion particles exposure. We summarize present knowledge from existing human epidemiological and clinical studies as well as experimental studies in animals and relevant in vitro studies. The available evidence suggests that organic compounds attached to these particles are significant triggers of CVD. Furthermore, their effects seem to be mediated at least in part by the aryl hydrocarbon receptor (AhR). The mechanisms include AhR-induced changes in gene expression as well as formation of reactive oxygen species (ROS) and/or reactive electrophilic metabolites. This is in accordance with a role of PAHs, as they seem to be the major chemical group on combustion particles, which bind AhR and/or is metabolically activated by CYP-enzymes. In some experimental models however, it seems as PAHs may induce an inflammatory atherosclerotic plaque phenotype irrespective of DNA- and/or AhR-ligand binding properties. Thus, various components and several signalling mechanisms/pathways are likely involved in CVD induced by combustion particles. We still need to expand our knowledge about the role of PAHs in CVD and in particular the relative importance of the different PAH species. This warrants further studies as enhanced knowledge on this issue may amend risk assessment of CVD caused by combustion particles and selection of efficient measures to reduce the health effects of particular matters (PM).

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“…Thus, it is conceivable that air pollution exposure, which causes irritation, alteration in breathing, and subsequent inflammation, directly or indirectly involves the activity of these receptors. However, until recently, only a few studies have examined the role of ARs or GRs in mediating the health effects of air pollution [3][4][5][6][7]. Some studies have assessed the contributions of ARs to pulmonary inflammation [8], whereas others have examined their role in the cardiovascular health effects of air pollutants [9].…”

Section: Introductionmentioning

confidence: 99%

Adrenergic and Glucocorticoid Receptors in the Pulmonary Health Effects of Air Pollution

Hodge

Henriquez

Kodavanti

2021

Toxics

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Adrenergic receptors (ARs) and glucocorticoid receptors (GRs) are activated by circulating catecholamines and glucocorticoids, respectively. These receptors regulate the homeostasis of physiological processes with specificity via multiple receptor subtypes, wide tissue-specific distribution, and interactions with other receptors and signaling processes. Based on their physiological roles, ARs and GRs are widely manipulated therapeutically for chronic diseases. Although these receptors play key roles in inflammatory and cellular homeostatic processes, little research has addressed their involvement in the health effects of air pollution. We have recently demonstrated that ozone, a prototypic air pollutant, mediates pulmonary and systemic effects through the activation of these receptors. A single exposure to ozone induces the sympathetic–adrenal–medullary and hypothalamic–pituitary–adrenal axes, resulting in the release of epinephrine and corticosterone into the circulation. These hormones act as ligands for ARs and GRs. The roles of beta AR (βARs) and GRs in ozone-induced pulmonary injury and inflammation were confirmed in a number of studies using interventional approaches. Accordingly, the activation status of ARs and GRs is critical in mediating the health effects of inhaled irritants. In this paper, we review the cellular distribution and functions of ARs and GRs, their lung-specific localization, and their involvement in ozone-induced health effects, in order to capture attention for future research.

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Organic chemicals from diesel exhaust particles affects intracellular calcium, inflammation and β-adrenoceptors in endothelial cells

Cited by 12 publications

References 60 publications

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Lipophilic Chemicals from Diesel Exhaust Particles Trigger Calcium Response in Human Endothelial Cells via Aryl Hydrocarbon Receptor Non-Genomic Signalling

Potential role of polycyclic aromatic hydrocarbons as mediators of cardiovascular effects from combustion particles

Adrenergic and Glucocorticoid Receptors in the Pulmonary Health Effects of Air Pollution

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