Disruption of sphingolipid and glycosphingolipid profiles in human bronchial epithelial cells and extracellular vesicles during gradual benzo[a]pyrene-induced epithelial-to-mesenchymal transition

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F25%3AN0000208" target="_blank" >RIV/00027162:_____/25:N0000208 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/68081707:_____/25:00641691

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0013935125019516?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0013935125019516?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.envres.2025.122699" target="_blank" >10.1016/j.envres.2025.122699</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Disruption of sphingolipid and glycosphingolipid profiles in human bronchial epithelial cells and extracellular vesicles during gradual benzo[a]pyrene-induced epithelial-to-mesenchymal transition

Popis výsledku v původním jazyce

In this study, effects of environmental carcinogen benzo[a]pyrene (BaP) on deregulation of sphingolipid (SL) and glycosphingolipid (GSL) metabolism were studied during BaP-induced transformation of normal human bronchial epithelial HBEC-12KT cells. After 2-weeks of exposure, BaP altered their morphology, while it downregulated sphingosine-1-phosphate (S1P) and upregulated sphingosine, gangliosides, GM3 and Lc3 GSLs. A longer, 8-week exposure to BaP, further increased cell migratory capacity, induced epithelial-to-mesenchymal transition (EMT) markers and EMT-related transcriptional regulators (SNAI1, ZEB1 and ZEB2), and it increased intracellular sphingosine, ceramide-1-phosphate, as well as a series of GSLs (glucosylceramide, lactosylceramide, GM1a, GD3, Lc3 and Gb3). A distinct profile of SL/GSL levels was observed in fully transformed cells established via exposure to BaP for 12 weeks. Increased sphingosine, S1P, ceramide-1-phosphate, GD3, Lc3 and Gb3 levels were paralleled by a decrease of other SL/GSLs, including GM3 pathway. These alterations were also partly reflected within extracellular vesicles and microvesicles, particularly in those released from fully transformed cells. Significantly altered enzymes of SL/GSL metabolism included a downregulation of S1P lyase and increased S1P, downregulation of GM-synthetic enzymes, and upregulation of enzymes of GD3 and Gb3 synthesis. Using siRNA-mediated knockdown of individual EMT transcriptional regulators, we then found them to play only a partial role in regulation of S1P, GM, GD3, Lc3 or Gb3, via deregulation of expression of the respective enzymes, suggesting that their enzymatic activities can be regulated also by other mechanisms. The mechanisms underlying deregulation of SL/GSL levels elicited by carcinogenic environmental pollutants and functions of individual SL/GSL species deserve further attention.

Název v anglickém jazyce

Disruption of sphingolipid and glycosphingolipid profiles in human bronchial epithelial cells and extracellular vesicles during gradual benzo[a]pyrene-induced epithelial-to-mesenchymal transition

Popis výsledku anglicky

In this study, effects of environmental carcinogen benzo[a]pyrene (BaP) on deregulation of sphingolipid (SL) and glycosphingolipid (GSL) metabolism were studied during BaP-induced transformation of normal human bronchial epithelial HBEC-12KT cells. After 2-weeks of exposure, BaP altered their morphology, while it downregulated sphingosine-1-phosphate (S1P) and upregulated sphingosine, gangliosides, GM3 and Lc3 GSLs. A longer, 8-week exposure to BaP, further increased cell migratory capacity, induced epithelial-to-mesenchymal transition (EMT) markers and EMT-related transcriptional regulators (SNAI1, ZEB1 and ZEB2), and it increased intracellular sphingosine, ceramide-1-phosphate, as well as a series of GSLs (glucosylceramide, lactosylceramide, GM1a, GD3, Lc3 and Gb3). A distinct profile of SL/GSL levels was observed in fully transformed cells established via exposure to BaP for 12 weeks. Increased sphingosine, S1P, ceramide-1-phosphate, GD3, Lc3 and Gb3 levels were paralleled by a decrease of other SL/GSLs, including GM3 pathway. These alterations were also partly reflected within extracellular vesicles and microvesicles, particularly in those released from fully transformed cells. Significantly altered enzymes of SL/GSL metabolism included a downregulation of S1P lyase and increased S1P, downregulation of GM-synthetic enzymes, and upregulation of enzymes of GD3 and Gb3 synthesis. Using siRNA-mediated knockdown of individual EMT transcriptional regulators, we then found them to play only a partial role in regulation of S1P, GM, GD3, Lc3 or Gb3, via deregulation of expression of the respective enzymes, suggesting that their enzymatic activities can be regulated also by other mechanisms. The mechanisms underlying deregulation of SL/GSL levels elicited by carcinogenic environmental pollutants and functions of individual SL/GSL species deserve further attention.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10620 - Other biological topics

Projekt

<a href="/cs/project/GA24-10086S" target="_blank" >GA24-10086S: Dopady působení polycyklických aromatických uhlovodíků na buněčné procesy spojené se stresovou signalizací a deregulací metabolismu</a><br>

Návaznosti

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

Rok uplatnění

2025

Kód důvěrnosti údajů

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

Název periodika

Environmental Research

ISSN

0013-9351

e-ISSN

1096-0953

Svazek periodika

285

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

US - Spojené státy americké

Počet stran výsledku

13

Strana od-do

—

Kód UT WoS článku

001566881200003

EID výsledku v databázi Scopus

2-s2.0-105014736063