PCB 153-induced changes in sphingolipid metabolism are potentially linked with alterations of intercellular communication in a model of non-tumorigenic rat liver epithelial cells

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F19%3AN0000251" target="_blank" >RIV/00027162:_____/19:N0000251 - isvavai.cz</a>

Result on the web

<a href="https://repozytorium.bg.ug.edu.pl/info/book/UOGbb29dabe4a6b4e3eaf9725b7466f7cd5/Dioxin+2018+Krak%25C3%25B3w+abstracts+book%253A+38th+International+Symposium+on+Halogenated+Persistent+Organic++Pollutants+%2526+10th+International+PCB+Workshop%252C+26-" target="_blank" >https://repozytorium.bg.ug.edu.pl/info/book/UOGbb29dabe4a6b4e3eaf9725b7466f7cd5/Dioxin+2018+Krak%25C3%25B3w+abstracts+book%253A+38th+International+Symposium+on+Halogenated+Persistent+Organic++Pollutants+%2526+10th+International+PCB+Workshop%252C+26-</a>

DOI - Digital Object Identifier

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Result language

angličtina

Original language name

PCB 153-induced changes in sphingolipid metabolism are potentially linked with alterations of intercellular communication in a model of non-tumorigenic rat liver epithelial cells

Original language description

38th International Symposium on Halogenated Persistent Organic Pollutants & 10th International PCB Workshop, 26-31 August 2018, Kraków, Poland – poster. PCB 153 (2,2´,4,4´,5,5´-hexachlorobiphenyl) is a highly abundant persistent PCB congener found both in the environment and in living organisms. Previously, we have observed that PCB 153 can modify sphingolipid metabolism in rat liver progenitor-like WB-F344 cells. In this study, possible mechanisms of the PCB 153-induced alterations of lipid species were examined, and possible links to significant cellular effects of PCB 153, such as inhibition of gap junctional intercellular communication (GJIC) and autophagy, were studied. Methods: LC/MS-MS, Western blotting, RT-PCR. Results: PCB 153 decreased intracellular ceramide and hexosylceramide levels, while simultaneously increasing the levels of dihydroceramide, dihydrosphingomyelin and dihydrosphingosin after 3h exposure of WB-F344 cells. PCB 153 inhibited dihydroceramide desaturase (DES1), which might be responsible for the observed disruption of ceramide synthetic pathway. In contrast, 24h-treatment with PCB 153 increased concentration of both dihydrosphingolipids and ceramides, suggesting a more complex, dynamic deregulation of sphingolipid metabolism, possibly involving e.g. modulation of sphingomyelinase activity. We have reported earlier that PCB 153 induced both acute and long-term inhibition of GJIC, the latter effect being accompanied with a decrease of phosphorylated forms of connexin 43 (Cx43), principle protein forming gap junctions in WB-F344. Inhibition of DES1 with a specific XM462 inhibitor mimicked the effect of PCB 153 on Cx43 protein. Autophagy is one of the possible degradation pathways of Cx43. We found that PCB 153 increased level of autophagy marker, LC3B-II. However, cotreatment of PCB 153 with spautin, an autophagy inhibitor, did not prevent PCB 153-induced changes in Cx43 level. Furthermore, DES inhibition and subsequent increase in dihydroceramide did not lead to an increase of LC3B-II. Conclusions: PCB 153 inhibits DES1 and increases dihydrosphingolipid intracellular concentrations, which could be linked to downregulation of Cx43 and inhibition of GJIC. Increased levels of autophagy marker LC3B-II are not involved in GJIC inhibition and probably not related to the observed increase in dihydrosphingolipids.

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/GA17-27669S" target="_blank" >GA17-27669S: Toxicolipidomics: emerging pathways of toxicity of organic pollutants</a><br>

Continuities

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

Publication year

2019

Confidentiality

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