Perturbations of sphingolipid metabolism induced by environmental chemicals in in vitro models of neural cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F20%3AN0000210" target="_blank" >RIV/00027162:_____/20:N0000210 - isvavai.cz</a>

Result on the web

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DOI - Digital Object Identifier

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Result language

angličtina

Original language name

Perturbations of sphingolipid metabolism induced by environmental chemicals in in vitro models of neural cells

Original language description

Sphingolipids (SL) are bioactive molecules with multiple structural and functional roles in neural cells. We therefore decided to describe perturbations of SL metabolism induced by model environmental neurotoxicants (ENTs) 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 3,3´-dichlorobiphenyl (PCB11) and 2,2',4,4',5,5'-hexachlorobiphenyl (PCB153). Changes in SL metabolism were analysed in 3 functionally distinct in vitro systems of neural cells: mouse neuroectodermal progenitors NE4C, human neuroblastoma cells SK-N-SH and human glial (oligodendrocytic) cells MO3.13. In vitro cell systems were exposed to model ENTs for 24h and their effects on mitochondrial activity (WST-1 assay), SL species composition (LC-MS/MS; 50 species) and on gene expression associated with SL metabolism (Custom PCR array) were analysed. WST-1 assay confirmed generally low potential of tested ENTs to induce acute changes in viability of neural cell lines. On the other hand, analysis of SL species revealed differences in sensitivity of tested cell lines to model ENTs and in spectrum of deregulated SLs. In SK-N-SH cells, mainly PCB153 triggered numerous alternations in SL ratios e.g. increase of LacCer/HexCer or decrease of HexCer/Cer. NE4C neural progenitors were the most sensitive cell line to tested ENTs, with PCB11 inducing the majority of detected alternations of SL ratios in these cells. Additionally, all tested compounds induced remarkable and uniform decrease in ceramide-1-phosphate levels in NE4C. Alternations of SL composition in oligodendrocytic precursors MO3.13 were observed preferentially for PCB153. Custom universal probe library (UPL) PCR array (120 genes) analysis of gene expression associated with SL metabolism revealed, that changes in SL composition are only partially reflected in SL-related transcriptome of exposed cells and correspond rather inversely with observed alterations of SL species levels, probably as a result of adaptive feedback loop to SL imbalance.

Czech name

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Czech description

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Type

O - Miscellaneous

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

<a href="/en/project/EF15_003%2F0000495" target="_blank" >EF15_003/0000495: FIT (Pharmacology, Immunotherapy, nanoToxicology)</a><br>

Continuities

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

Publication year

2020

Confidentiality

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