Effects of complex airborne environmental mixtures on sphingolipid and eicosanoid composition in human bronchial epithelial cells

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F23%3AN0000105" target="_blank" >RIV/00027162:_____/23:N0000105 - isvavai.cz</a>

Výsledek na webu

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DOI - Digital Object Identifier

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Jazyk výsledku

angličtina

Název v původním jazyce

Effects of complex airborne environmental mixtures on sphingolipid and eicosanoid composition in human bronchial epithelial cells

Popis výsledku v původním jazyce

Oral presentation. In: Genetická toxikológia a prevencia rakoviny, Smolenice, Slovensko, 12.-15.6.2023, p. 14. The toxic effects of airborne particles have been evaluated in numerous studies. Profiling of airborne particles and their organic extracts has revealed multiple types of adverse effects, including activation of aryl hydrocarbon receptor (AhR), induction of xenobiotic-metabolizing enzymes, various oxidative, genotoxic and mutagenic effects, inflammatory responses, or cell death. Sphingolipids (SLs) and glycosphingolipids (GSLs) are known as important structural components of cell membranes, including lipid rafts, as well as bioactive lipid signaling molecules playing numerous roles in cell (patho)physiology. SLs and GSLs can regulate cell growth, proliferation, survival, senescence, apoptosis, as well as the processes linked with cancer progression. In this study, we used human bronchial epithelial HBEC-12KT cells in order to study the effects of complex organic mixtures derived from standard reference material representing urban airborne particles (SRM1649b). We combined the analyses of the effects of crude extract (CE) with the evaluation of the impact of its chromatographic fractions (F1-3) in cytotoxic and non-cytotoxic concentrations after 24-hour exposure. We examined the effects on SL/GSL and eicosanoid levels, expression of the genes linked to lipid metabolism and cell cycle distribution. The cytotoxic concentrations of CE and F3 have shown significantly higher AhR activity, resulting in induced degradation of AhR. Metabolites from the AhR metabolomic pathway were observed to have a genotoxic effect by decreasing p21 protein levels, a protein responsible for cell cycle arrest, and an increase in DNA damage marker - histone H2AX, indicating more extensive DNA damage. Next, we investigated the deviations in SL/GSL metabolism. We found a significant increase in dihydroceramides (dhCer) and ceramides, and also a significant decrease in sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), accompanied by the deregulations of expressions of some corresponding genes (CERS2, ASAH1, CERK). This switch in the ratio of Cer/S1P plus an increase of dhCer could indicate a shift towards apoptosis. We also detected changes in GSL, both hexosylceramides and lactosylceramides were suppressed. These alterations were predominantly observed in the cytotoxic concentrations of CE and F3, but to a certain extent, similar changes were also observed in the non-cytotoxic concentrations. Altogether, we have observed genotoxic effects, extensive changes in the SL/GSL metabolism, expression of linked genes after the exposure, suggesting that the organic extracts of SRM1694b in cytotoxic concentrations cause strong adverse effects in cells and shift the cell machinery towards cell death.

Název v anglickém jazyce

Effects of complex airborne environmental mixtures on sphingolipid and eicosanoid composition in human bronchial epithelial cells

Popis výsledku anglicky

Oral presentation. In: Genetická toxikológia a prevencia rakoviny, Smolenice, Slovensko, 12.-15.6.2023, p. 14. The toxic effects of airborne particles have been evaluated in numerous studies. Profiling of airborne particles and their organic extracts has revealed multiple types of adverse effects, including activation of aryl hydrocarbon receptor (AhR), induction of xenobiotic-metabolizing enzymes, various oxidative, genotoxic and mutagenic effects, inflammatory responses, or cell death. Sphingolipids (SLs) and glycosphingolipids (GSLs) are known as important structural components of cell membranes, including lipid rafts, as well as bioactive lipid signaling molecules playing numerous roles in cell (patho)physiology. SLs and GSLs can regulate cell growth, proliferation, survival, senescence, apoptosis, as well as the processes linked with cancer progression. In this study, we used human bronchial epithelial HBEC-12KT cells in order to study the effects of complex organic mixtures derived from standard reference material representing urban airborne particles (SRM1649b). We combined the analyses of the effects of crude extract (CE) with the evaluation of the impact of its chromatographic fractions (F1-3) in cytotoxic and non-cytotoxic concentrations after 24-hour exposure. We examined the effects on SL/GSL and eicosanoid levels, expression of the genes linked to lipid metabolism and cell cycle distribution. The cytotoxic concentrations of CE and F3 have shown significantly higher AhR activity, resulting in induced degradation of AhR. Metabolites from the AhR metabolomic pathway were observed to have a genotoxic effect by decreasing p21 protein levels, a protein responsible for cell cycle arrest, and an increase in DNA damage marker - histone H2AX, indicating more extensive DNA damage. Next, we investigated the deviations in SL/GSL metabolism. We found a significant increase in dihydroceramides (dhCer) and ceramides, and also a significant decrease in sphingosine-1-phosphate (S1P) and ceramide-1-phosphate (C1P), accompanied by the deregulations of expressions of some corresponding genes (CERS2, ASAH1, CERK). This switch in the ratio of Cer/S1P plus an increase of dhCer could indicate a shift towards apoptosis. We also detected changes in GSL, both hexosylceramides and lactosylceramides were suppressed. These alterations were predominantly observed in the cytotoxic concentrations of CE and F3, but to a certain extent, similar changes were also observed in the non-cytotoxic concentrations. Altogether, we have observed genotoxic effects, extensive changes in the SL/GSL metabolism, expression of linked genes after the exposure, suggesting that the organic extracts of SRM1694b in cytotoxic concentrations cause strong adverse effects in cells and shift the cell machinery towards cell death.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GA17-27669S" target="_blank" >GA17-27669S: Toxikolipidomika: nové mechanismy toxicity organických polutantů</a><br>

Návaznosti

P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů