Modulation of sphingolipid metabolism and gene expression in undifferentiated and differentiated heparg cells exposed to TCDD

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F20%3AN0000211" target="_blank" >RIV/00027162:_____/20:N0000211 - 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

Modulation of sphingolipid metabolism and gene expression in undifferentiated and differentiated heparg cells exposed to TCDD

Popis výsledku v původním jazyce

Sphingolipids are bioactive lipids, important structural components of cellular membranes, lipid rafts and also significant modulators of intracellular signal pathways. Their crucial role consist in cell survival, signal transduction and cell to cell communication. However, modulation of sphingolipid metabolism, especially by organic xenobiotics, is still poorly understood. In this study, we use differentiated and undifferentiated HepaRG cell line, as a model of human-live progenitor cells and exposed them to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We had determined possible impact of this compound on sphingolipid metabolism and on expression of genes linked to sphingolipid metabolism. TCDD is persistent environmental pollutant and human carcinogen which toxicity is induced via activation of aryl hydrocarbon receptor (AhR). HepaRG cells exposed to 1nM or 10nM TCDD showed increased production of glycosphingolipids (especially glucoceramide) and dihydroceramides (undifferentiated cells) in comparison to the untreated-control group. Gene expression analysis showed deregulated mRNA expression of specific genes of sphingolipid metabolism. For example, upregulated expression of UGCG gene coincided with observed enhancement of glucoceramide synthesis.

Název v anglickém jazyce

Modulation of sphingolipid metabolism and gene expression in undifferentiated and differentiated heparg cells exposed to TCDD

Popis výsledku anglicky

Sphingolipids are bioactive lipids, important structural components of cellular membranes, lipid rafts and also significant modulators of intracellular signal pathways. Their crucial role consist in cell survival, signal transduction and cell to cell communication. However, modulation of sphingolipid metabolism, especially by organic xenobiotics, is still poorly understood. In this study, we use differentiated and undifferentiated HepaRG cell line, as a model of human-live progenitor cells and exposed them to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). We had determined possible impact of this compound on sphingolipid metabolism and on expression of genes linked to sphingolipid metabolism. TCDD is persistent environmental pollutant and human carcinogen which toxicity is induced via activation of aryl hydrocarbon receptor (AhR). HepaRG cells exposed to 1nM or 10nM TCDD showed increased production of glycosphingolipids (especially glucoceramide) and dihydroceramides (undifferentiated cells) in comparison to the untreated-control group. Gene expression analysis showed deregulated mRNA expression of specific genes of sphingolipid metabolism. For example, upregulated expression of UGCG gene coincided with observed enhancement of glucoceramide synthesis.

Druh

O - Ostatní výsledky

CEP obor

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OECD FORD obor

30108 - Toxicology

Projekt

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Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2020

Kód důvěrnosti údajů

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