DNA methylation and RASSF4 expression are involved in T-2 toxin-induced hepatotoxicity

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F19%3A50017602" target="_blank" >RIV/62690094:18470/19:50017602 - isvavai.cz</a>

Výsledek na webu

<a href="https://www.sciencedirect.com/science/article/pii/S0300483X19302021?via%3Dihub" target="_blank" >https://www.sciencedirect.com/science/article/pii/S0300483X19302021?via%3Dihub</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2019.152246" target="_blank" >10.1016/j.tox.2019.152246</a>

Jazyk výsledku

angličtina

Název v původním jazyce

DNA methylation and RASSF4 expression are involved in T-2 toxin-induced hepatotoxicity

Popis výsledku v původním jazyce

T-2 toxin is a secondary metabolite produced by Fusarium species and commonly contaminates food and animal feed. T-2 toxin can induce hepatotoxicity through apoptosis and oxidative stress; however, the underlying mechanism is not clear. Recent studies indicated that RASSF4, a member of the RASSF family, participates in cell apoptosis and some cancers due to its inactivation via DNA hypermethylation. However, its role in T-2 toxininduced liver toxicity is poorly understood. Therefore, in this study, female Wistar rats were given a single dose of T-2 toxin at 2 mg/kg b.w. and were sacrificed at 1, 3 and 7 days post-exposure. A normal rat liver cell line (BRL) was exposed to different concentrations of T-2 toxin (10, 20, 40 nM) for 4, 8, 12 h, respectively. Histopathological analysis revealed with apoptosis in some liver cells and clear proliferation under T-2 toxin exposure. Expression analysis by immunohistochemical assays, quantitative real-time PCR (qPCR) and westem blot demonstrated that T-2 toxin activated PI3K-Akt/Caspase/NF-kappa B signaling pathways. Additionally, DNA methylation assays revealed that the expression of RASSF4 was silenced by promoter hypermethylation after exposure to T-2 toxin for 1 and 3 days as compared to the control group. Moreover, joint treatment of 5-Aza-2&apos;-deoxycytidine (DAC) (5 mu M) and T-2 toxin (40 nM) increased expression of RASSF4 and PI3K-Akt/caspase/NF-kappa B signaling pathways-related genes, inducing cell apoptosis. These findings for the first time demonstrated that DNA methylation regulated the RASSF4 expression under T-2 toxin, along with the activation of its downstream pathways, resulting in apoptosis.

Název v anglickém jazyce

DNA methylation and RASSF4 expression are involved in T-2 toxin-induced hepatotoxicity

Popis výsledku anglicky

T-2 toxin is a secondary metabolite produced by Fusarium species and commonly contaminates food and animal feed. T-2 toxin can induce hepatotoxicity through apoptosis and oxidative stress; however, the underlying mechanism is not clear. Recent studies indicated that RASSF4, a member of the RASSF family, participates in cell apoptosis and some cancers due to its inactivation via DNA hypermethylation. However, its role in T-2 toxininduced liver toxicity is poorly understood. Therefore, in this study, female Wistar rats were given a single dose of T-2 toxin at 2 mg/kg b.w. and were sacrificed at 1, 3 and 7 days post-exposure. A normal rat liver cell line (BRL) was exposed to different concentrations of T-2 toxin (10, 20, 40 nM) for 4, 8, 12 h, respectively. Histopathological analysis revealed with apoptosis in some liver cells and clear proliferation under T-2 toxin exposure. Expression analysis by immunohistochemical assays, quantitative real-time PCR (qPCR) and westem blot demonstrated that T-2 toxin activated PI3K-Akt/Caspase/NF-kappa B signaling pathways. Additionally, DNA methylation assays revealed that the expression of RASSF4 was silenced by promoter hypermethylation after exposure to T-2 toxin for 1 and 3 days as compared to the control group. Moreover, joint treatment of 5-Aza-2&apos;-deoxycytidine (DAC) (5 mu M) and T-2 toxin (40 nM) increased expression of RASSF4 and PI3K-Akt/caspase/NF-kappa B signaling pathways-related genes, inducing cell apoptosis. These findings for the first time demonstrated that DNA methylation regulated the RASSF4 expression under T-2 toxin, along with the activation of its downstream pathways, resulting in apoptosis.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

—

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2019

Kód důvěrnosti údajů

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

Název periodika

Toxicology

ISSN

0300-483X

e-ISSN

—

Svazek periodika

425

Číslo periodika v rámci svazku

SEP

Stát vydavatele periodika

IE - Irsko

Počet stran výsledku

11

Strana od-do

"Article Number: 152246"

Kód UT WoS článku

000484649700011

EID výsledku v databázi Scopus

2-s2.0-85069944290