Could changes in sphingolipid metabolism/transcriptome reflect neurotoxicity of environmental pollutants?

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00027162%3A_____%2F19%3AN0000281" target="_blank" >RIV/00027162:_____/19:N0000281 - isvavai.cz</a>

Result on the web

—

DOI - Digital Object Identifier

—

Result language

angličtina

Original language name

Could changes in sphingolipid metabolism/transcriptome reflect neurotoxicity of environmental pollutants?

Original language description

FEBS - Sphingolipid Biology: Sphingolipids in Physiology and Pathology, 6.-10.5.2019, Cascais, Portugal – poster. Persistent organic pollutants are routinely spread over the large areas worldwide and accumulation of their levels in our environment represent one of the major health safety problem as degradation rate of these compounds is generally rather low and occurs in range of decades. Byproducts generated during industrial manufacturing (e.g. dioxins) as well as intentionally produced industrial chemicals (e.g. polychlorinated biphenyls) are known carcinogens and neurotoxic chemicals. However, mechanisms of their action leading to neurotoxicity are poorly characterized. We used 2,3,7,8tetrachlorodibenzopdioxin (TCDD) and 2,2´,4,4´,5,5´hexachlorobiphenyl (PCB153) as prototypical persistent toxicants for establishment of in vitro models suitable for testing neurotoxicity. In the first part of study, we employed undifferentiated murine neuroectodermal NE4C cells and human neuroblastoma SKNSH cells and exposed them for 24h to tested compounds. Our preliminary data show changes in sphingolipid (SL) metabolism after TCDD treatment, especially at the levels of hexosylceramide, sphingosine and dihydrosphingosine. Besides, we monitored expression levels of genes, which protein products are involved in sphingolipid metabolism using custom PCR array of 120 human genes of SL and cholesterol metabolism. In the second part of study, we simulated neurogenesis using retinoic acid (RA)induced differentiation of NE4C cells chronically exposed to TCDD, PCB153 or vehicle (DMSO) in order to describe changes in SL metabolism. Compilation of data from undifferentiated cells and their differentiated progeny may help to better understand whether changes in SL metabolism induced by toxic stress in undifferentiated neural cells could reflect and predict defects in their differentiated progeny during chemically disrupted neurogenesis.

Czech name

—

Czech description

—

Type

O - Miscellaneous

CEP classification

—

OECD FORD branch

10601 - Cell biology

Project

Result was created during the realization of more than one project. More information in the Projects tab.

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