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@article{1300506,
author = {Svobodová, Jana and Kabátková, Markéta and Šmerdová, Lenka and Brenerová, Petra and Dvořák, Zdeněk and Machala, Miroslav and Vondráček, Jan},
article_location = {Clare, Ireland},
article_number = {July},
doi = {http://dx.doi.org/10.1016/j.tox.2015.04.001},
keywords = {AhR; TCDD; BIRC5/survivin; Contact inhibition; Apoptosis; Hippo signaling},
language = {eng},
issn = {0300-483X},
journal = {Toxicology},
title = {The aryl hydrocarbon receptor-dependent disruption of contact inhibition in rat liver WB-F344 epithelial cells is linked with induction of survivin, but not with inhibition of apoptosis},
url = {http://www.sciencedirect.com/science/article/pii/S0300483X15000633},
volume = {333},
year = {2015}
}
TY - JOUR
ID - 1300506
AU - Svobodová, Jana - Kabátková, Markéta - Šmerdová, Lenka - Brenerová, Petra - Dvořák, Zdeněk - Machala, Miroslav - Vondráček, Jan
PY - 2015
TI - The aryl hydrocarbon receptor-dependent disruption of contact inhibition in rat liver WB-F344 epithelial cells is linked with induction of survivin, but not with inhibition of apoptosis
JF - Toxicology
VL - 333
IS - July
SP - 37-44
EP - 37-44
PB - Elsevier Sci Ireland Ltd
SN - 0300483X
KW - AhR
KW - TCDD
KW - BIRC5/survivin
KW - Contact inhibition
KW - Apoptosis
KW - Hippo signaling
UR - http://www.sciencedirect.com/science/article/pii/S0300483X15000633
N2 - Inhibition of apoptosis by the ligands of the aryl hydrocarbon receptor (AhR) has been proposed to play a role in their tumor promoting effects on liver parenchymal cells. However, little is presently known about the impact of toxic AhR ligands, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on apoptosis in other liver cell types, such as in liver epithelial/progenitor cells. In the present study, we focused on the effects of TCDD on apoptosis regulation in a model of liver progenitor cells, rat WB-F344 cell line, during the TCDD-elicited release from contact inhibition. The stimulation of cell proliferation in this cell line was associated with deregulated expression of a number of genes known to be under transcriptional control of the Hippo signaling pathway, a principal regulatory pathway involved in contact inhibition of cell proliferation. Interestingly, we found that mRNA and protein levels of survivin, a known Hippo target, which plays a role both in cell division and inhibition of apoptosis, were significantly up-regulated in rat liver epithelial cell model, as well as in undifferentiated human liver HepaRG cells. Using the short interfering RNA-mediated knockdown, we confirmed that survivin plays a central role in cell division of WB-F344 cells. When evaluating the effects of TCDD on apoptosis induction by camptothecin, a genotoxic topoisomerase I inhibitor, we observed that the pre-treatment of WB-F344 cells with TCDD increased number of cells with apoptotic nuclear morphology, and it potentiated cleavage of both caspase-3 and poly(ADP-ribose) polymerase I. This indicated that despite the observed up-regulation of survivin, apoptosis induced by the genotoxin was potentiated in the model of rat liver progenitor cells. The present results indicate that, unlike in hepatocytes, AhR agonists may not prevent induction of apoptosis elicited by DNA-damaging agents in a model of rat liver progenitor cells
ER -
SVOBODOVÁ, Jana, Markéta KABÁTKOVÁ, Lenka ŠMERDOVÁ, Petra BRENEROVÁ, Zdeněk DVOŘÁK, Miroslav MACHALA and Jan VONDRÁČEK. The aryl hydrocarbon receptor-dependent disruption of contact inhibition in rat liver WB-F344 epithelial cells is linked with induction of survivin, but not with inhibition of apoptosis. \textit{Toxicology}. Clare, Ireland: Elsevier Sci Ireland Ltd, 2015, vol.~333, July, p.~37-44. ISSN~0300-483X. Available from: https://dx.doi.org/10.1016/j.tox.2015.04.001.
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