The critical role of p16/Rb pathway in the inhibition of GH3 cell cycle induced by T-2 toxin

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F62690094%3A18470%2F18%3A50014828" target="_blank" >RIV/62690094:18470/18:50014828 - isvavai.cz</a>

Result on the web

<a href="http://dx.doi.org/10.1016/j.tox.2018.03.006" target="_blank" >http://dx.doi.org/10.1016/j.tox.2018.03.006</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.tox.2018.03.006" target="_blank" >10.1016/j.tox.2018.03.006</a>

Result language

angličtina

Original language name

The critical role of p16/Rb pathway in the inhibition of GH3 cell cycle induced by T-2 toxin

Original language description

T-2 toxin is a worldwide trichothecenetoxin and can cause various toxicities.T-2 toxin is involved in G1 phase arrest in several cell lines but molecular mechanism is still not clear. In present study, we used rat pituitary GH3 cells to investigate the mechanism involved in cell cycle arrest against T-2 toxin (40 nM) for 12, 24, 36 and 48 h as compared to control cells. GH3 cells showed a considerable increase in reactive oxygen species (ROS) as well as loss in mitochondrial membrane potential (Delta Ym) upon exposure to the T-2 toxin. Flow cytometry showed a significant time-dependent increase in percentage of apoptotic cells and gel electrophoresis showed the hallmark of apoptosis oligonucleosomal DNA fragmentation. Additionally, T-2 toxin-induced oxidative stress and DNA damage with a time-dependent significant increased expression of p53 favors the apoptotic process by the activation of caspase-3 in T-2 toxin treated cells. Cell cycle analysis by flow cytometry revealed a time-dependent increase of Gl cell population along with the significant time-dependent up-regulation of mRNA and protein expression of p16 and p21 and significant down-regulation of cyclin D1, CDK4, and p-RB levels further verify the G1 phase arrest in GH3 cells. Morphology of GH3 cells by TEM clearly showed the damage and dysfunction to mitochondria and the cell nucleus. These findings for the first time demonstrate that T-2 toxin induces G1 phase cell cycle arrest by the involvement of p16/Rb pathway, along with ROS mediated oxidative stress and DNA damage with p53 and caspase cascade interaction, resulting in apoptosis in GH3 cells.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30108 - Toxicology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

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

Name of the periodical

Toxicology

ISSN

0300-483X

e-ISSN

—

Volume of the periodical

400

Issue of the periodical within the volume

May

Country of publishing house

IE - IRELAND

Number of pages

12

Pages from-to

28-39

UT code for WoS article

000432617500004

EID of the result in the Scopus database

2-s2.0-85044102443