Home General Physiology and Biophysics 2018 General Physiology and Biophysics Vol.37, No.5, p.589–596, 2018

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Founded: 1982
ISSN 1338-4325 (online)
ISSN 0231-5882 (print)
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General Physiology and Biophysics Vol.37, No.5, p.589–596, 2018

Title: Effects of selected triorganotin compounds on transcriptional activity of vitamin D3 receptor and peroxisome proliferator-activated receptor gamma
Author: L. Toporova, P. Illes, Z. Dvorak, P. Bobal, J. Otevrel, J. Brtko
Abstract: 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.
Keywords: Triorganotin derivatives, Vitamin D3 receptor, Peroxisome proliferator-activated receptor, Transcriptional activity
Published online: 02-Oct-2018
Year: 2018, Volume: 37, Issue: 5 Page From: 589, Page To: 596
doi:10.4149/gpb_2018021


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