Effects of selected triorganotin compounds on transcriptional activity of vitamin D3 receptor and peroxisome proliferator-activated receptor gamma

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F61989592%3A15310%2F18%3A73588465" target="_blank" >RIV/61989592:15310/18:73588465 - isvavai.cz</a>

Nalezeny alternativní kódy

RIV/62157124:16370/18:43877070

Výsledek na webu

<a href="http://dx.doi.org/10.4149/gpb_2018021" target="_blank" >http://dx.doi.org/10.4149/gpb_2018021</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.4149/gpb_2018021" target="_blank" >10.4149/gpb_2018021</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Effects of selected triorganotin compounds on transcriptional activity of vitamin D3 receptor and peroxisome proliferator-activated receptor gamma

Popis výsledku v původním jazyce

Both, the vitamin D3 receptor (VDR) and the peroxisome proliferator-activated receptor gamma (PPARγ), are ligand-inducible transcription factors that control expressions of various genes involved in essential biological processes. Structurally diverse chemical substances are capable to bind to VDR and PPARγ, consequently acting in agonistic or antagonistic mode. Ubiquitous triorganotin compounds, key components of antifouling, disinfectant and biocidal agents were found to act as cognate ligands of several nuclear receptors. Triorganotins affect endocrine systems in disruptive manner recruiting proliferative, differentiation and apoptotic pathways. In this study, we have investigated agonistic as well as antagonistic effects of selected triorganotin compounds on VDR and PPARγ in transgenic gene reporter IZ-VDRE and PAZ-PPARγ human cell lines, allowing rapid and sensitive assessment of receptor transcriptional activity. We demonstrated that most of investigated triorganotins at nanomolar concentration exerted significant agonistic effects on VDR with fold activation ranging from 2.0 to 3.0-fold as well as some significant changes ranging from 127 to 199% of the maximal 1,25-dihydroxyvitamin D3 (calcitriol) induction, in antagonistic mode. In agonistic mode, PPARγ transcriptional activity was not affected by studied triorganotins significantly, but studied tributyltin compounds in antagonistic mode, revealed significant values ranging from 147 to 171% of the maximal 15-deoxy-δ12,14-prostaglandin J2 induction.

Název v anglickém jazyce

Effects of selected triorganotin compounds on transcriptional activity of vitamin D3 receptor and peroxisome proliferator-activated receptor gamma

Popis výsledku anglicky

Both, the vitamin D3 receptor (VDR) and the peroxisome proliferator-activated receptor gamma (PPARγ), are ligand-inducible transcription factors that control expressions of various genes involved in essential biological processes. Structurally diverse chemical substances are capable to bind to VDR and PPARγ, consequently acting in agonistic or antagonistic mode. Ubiquitous triorganotin compounds, key components of antifouling, disinfectant and biocidal agents were found to act as cognate ligands of several nuclear receptors. Triorganotins affect endocrine systems in disruptive manner recruiting proliferative, differentiation and apoptotic pathways. In this study, we have investigated agonistic as well as antagonistic effects of selected triorganotin compounds on VDR and PPARγ in transgenic gene reporter IZ-VDRE and PAZ-PPARγ human cell lines, allowing rapid and sensitive assessment of receptor transcriptional activity. We demonstrated that most of investigated triorganotins at nanomolar concentration exerted significant agonistic effects on VDR with fold activation ranging from 2.0 to 3.0-fold as well as some significant changes ranging from 127 to 199% of the maximal 1,25-dihydroxyvitamin D3 (calcitriol) induction, in antagonistic mode. In agonistic mode, PPARγ transcriptional activity was not affected by studied triorganotins significantly, but studied tributyltin compounds in antagonistic mode, revealed significant values ranging from 147 to 171% of the maximal 15-deoxy-δ12,14-prostaglandin J2 induction.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

30108 - Toxicology

Projekt

<a href="/cs/project/GA16-07544S" target="_blank" >GA16-07544S: Konstrukce in vitro modelů založených na reportérových buněčných liniích pro toxikologické a environmentální aplikace</a><br>

Návaznosti

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

Rok uplatnění

2018

Kód důvěrnosti údajů

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

Název periodika

GENERAL PHYSIOLOGY AND BIOPHYSICS

ISSN

0231-5882

e-ISSN

—

Svazek periodika

37

Číslo periodika v rámci svazku

5

Stát vydavatele periodika

SK - Slovenská republika

Počet stran výsledku

8

Strana od-do

589-596

Kód UT WoS článku

000448096800010

EID výsledku v databázi Scopus

2-s2.0-85054780536