Important key players in the regulatory machinery within the cells are nuclear retinoid X receptors (RXRs), which compose heterodimers in company with several diverse nuclear receptors, playing a role as ligand inducible transcription factors. In general, nuclear receptors are ligand-activated, transcription-modulating proteins affecting transcriptional responses in target genes. RXR molecules forming permissive heterodimers with disparate nuclear receptors comprise peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstan receptor (CAR). Retinoid receptors (RARs) and thyroid hormone receptors (TRs) may form conditional heterodimers, and dihydroxyvitamin D3 receptor (VDR) is believed to form nonpermissive heterodimer. Thus, RXRs are the important molecules that are involved in control of many cellular functions in biological processes and diseases, including cancer or diabetes. This article summarizes both naturally occurring and synthetic ligands for nuclear retinoid X receptors and describes, predominantly in mammals, their role in molecular mechanisms within the cells. A focus is also on triorganotin compounds, which are high affinity RXR ligands, and finally, we present an outlook on human microbiota as a potential source of RXR activators. Nevertheless, new synthetic rexinoids with better retinoid X receptor activity and lesser side effects are highly required.

• Klíčová slova
• Human microbiota, Ligand inducible transcription factors, Natural and synthetic RXR ligands, Nuclear receptors, Retinoid X receptors (RXR),
• MeSH
• lidé MeSH
• ligandy MeSH
• mikrobiota MeSH
• organocínové sloučeniny farmakologie   MeSH
• receptory cytoplazmatické a nukleární fyziologie   MeSH
• retinoidní X receptory agonisté   fyziologie   MeSH
• tretinoin analogy a deriváty   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• ligandy MeSH
• organocínové sloučeniny MeSH
• receptory cytoplazmatické a nukleární MeSH
• retinoidní X receptory MeSH
• tretinoin MeSH

The v-myb oncogene of avian myeloblastosis virus causes acute monoblastic leukemia in vivo and transforms myelomonocytic cells in culture. Retinoids are potent regulators of proliferation and differentiation in various cell types, and they can initiate differentiation in certain types of leukemic cells. However, the BM2 v-myb-transformed chicken monoblastic cell line is resistant to retinoic acid treatment. We found that overexpression of the retinoid X receptor confers sensitivity of BM2 cells to retinoic acid, resulting in induction of growth arrest and terminal differentiation. In contrast, the frequency of apoptosis was not affected by the retinoid X receptor in this cell type. We also demonstrated that suppression of transformation by v-Myb results from the negative effect of retinoid X receptor on v-Myb transactivation function, similar to that previously described for the retinoic acid receptor. The retinoid X receptor-induced inhibition of transactivation by v-Myb seems to be enhanced by a cell type-specific factor(s), which is not required by retinoic acid receptor.

• MeSH
• aktivace transkripce MeSH
• buněčná diferenciace genetika   MeSH
• buněčné dělení genetika   MeSH
• fibroblasty metabolismus   fyziologie   MeSH
• geny myb fyziologie   MeSH
• komplementární DNA biosyntéza   genetika   metabolismus   MeSH
• křepelky a křepelovití MeSH
• kur domácí MeSH
• lidé MeSH
• monocyty cytologie   účinky léků   metabolismus   fyziologie   MeSH
• nádorová transformace buněk genetika   MeSH
• receptory kyseliny retinové biosyntéza   klasifikace   genetika   fyziologie   MeSH
• regulace genové exprese MeSH
• retinoidní X receptory MeSH
• suprese genetická MeSH
• transfekce MeSH
• transformované buněčné linie MeSH
• transkripční faktory biosyntéza   klasifikace   genetika   fyziologie   MeSH
• virus ptačí myeloblastózy genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, P.H.S. MeSH
• Názvy látek
• komplementární DNA MeSH
• receptory kyseliny retinové MeSH
• retinoidní X receptory MeSH
• transkripční faktory MeSH

AIM: Polymorphisms in retinoid X receptors (RXRs) are very interesting from the point of view of a possible association of their variability with psoriasis. METHODS: A total of 293 patients with plaque psoriasis, 82 patients with psoriasis guttata and 202 control subjects were enrolled in this study focused on 3 polymorphisms in RXRA and RXRB gene associations. RESULTS: A marginally significant increase in AA allelic frequency of the RXRA A39526AA polymorphism in plaque psoriatic men compared to healthy men was proved. In women with psoriasis guttata, the higher risk for genotypes AA and TT in the RXRB 3'+140A/T polymorphism compared to healthy women was identified (p(corr) = 0.01). The genotypes A/A and AA/AA are more frequent in plaque psoriasis patients with a positive family history of psoriasis compared to the patients with a negative family history of psoriasis (p(corr) = 0.02). The A/A genotype is more frequent in patients with plaque psoriasis and repeated tonsillitis/tonsillectomy (p = 0.02). In the RXRB polymorphism, no genotype TT is observed in patients with psoriasis guttata with a positive personal history of repeated tonsillitis (p(corr) = 0.001). CONCLUSION: Individual gene characteristics of patients with psoriasis improve the possibilities of pharmacotherapy using pharmacogenomic approaches which could be further stratified in future according to the subtypes of psoriasis.

• MeSH
• angiotensinogen genetika   MeSH
• dospělí MeSH
• frekvence genu MeSH
• genotyp * MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA genetika   MeSH
• mladiství MeSH
• polymorfismus genetický * MeSH
• psoriáza klasifikace   genetika   patologie   MeSH
• retinoidní X receptor alfa genetika   MeSH
• retinoidní X receptor beta genetika   MeSH
• retinoidní X receptory genetika   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• tonzilitida genetika   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• angiotensinogen MeSH
• messenger RNA MeSH
• retinoidní X receptor alfa MeSH
• retinoidní X receptor beta MeSH
• retinoidní X receptory MeSH

Several commercially available triorganotin compounds were previously found to function as agonist ligands for nuclear retinoid X receptor (RXR) molecules. Triphenyltin isoselenocyanate (TPT-NCSe), a novel selenium atom containing a derivative of triorganotin origin, was found to represent a new cognate bioactive ligand for RXRs. TPT-NCSe displayed a concentration- and time-dependent decrease in the cell viability in both human breast carcinoma MCF-7 (estrogen receptor positive) and MDA‑MB‑231 (triple negative) cell lines. Reactive oxygen species levels generated in response to TPT-NCSe were significantly higher in both carcinoma cell lines treated with TPT-NCSe when compared to mock-treated samples. Treatment with 500 nM TPT-NCSe caused a decrease in SOD1 and increased SOD2 mRNA in MCF-7 cells. The levels of SOD2 mRNA were more increased following the treatment with TPT-NCSe along with 1 μM all-trans retinoic acid (AtRA) in MCF-7 cells. An increased superoxide dismutase SOD1 and SOD2 mRNA levels were also detected in combination treatment of 500 nM TPT-NCSe and 1 μM AtRA in TPT-NCSe-treated MDA-MB-231 cells. The data have also shown that TPT-NCSe induces apoptosis via a caspase cascade triggered by the mitochondrial apoptotic pathway. TPT-NCSe modulates the expression levels of apoptosis‑related proteins, Annexin A5, Bcl‑2 and BAX family proteins, and finally, it enhances the expression levels of its cognate nuclear receptor subtypes RXRalpha and RXRbeta.

• Klíčová slova
• Apoptosis, Breast cancer, Retinoid X receptor, Triorganotin isoselenocyanates,
• MeSH
• apoptóza účinky léků   MeSH
• lidé MeSH
• ligandy MeSH
• MFC-7 buňky MeSH
• nádorové buněčné linie MeSH
• nádory prsu * farmakoterapie   metabolismus   patologie   MeSH
• organocínové sloučeniny * farmakologie   MeSH
• organoselenové sloučeniny farmakologie   chemie   MeSH
• proliferace buněk účinky léků   MeSH
• reaktivní formy kyslíku metabolismus   MeSH
• retinoidní X receptory metabolismus   MeSH
• superoxiddismutasa 1 metabolismus   genetika   MeSH
• superoxiddismutasa metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• ligandy MeSH
• organocínové sloučeniny * MeSH
• organoselenové sloučeniny MeSH
• reaktivní formy kyslíku MeSH
• retinoidní X receptory MeSH
• SOD1 protein, human MeSH Prohlížeč
• superoxiddismutasa 1 MeSH
• superoxiddismutasa MeSH
• superoxide dismutase 2 MeSH Prohlížeč
• triphenyltin MeSH Prohlížeč

BACKGROUND: Renal cell carcinoma (RCC) is a urologic malignancy with a steady rise in incidence and high mortality rate. Between 60 to 70% of patients with renal cell carcinoma can only be cured with surgery but despite advances in early diagnostis, in around 20-30% of cases there is metastasis. For these patients, chemotherapy and radiotherapy are ineffective and hence the prognosis is poor. Retinoids are biologically active compounds of either natural or synthetic origin that are involved in complex physiological and developmental processes in many tissues including cell proliferation and activation of tumour suppression genes. This article reviews the role of retinoids and their cognate nuclear retinoid/rexinoid receptors in relation to renal cell carcinoma. METHODS: A literature search using ScienceDirect and Medline with a focus on the relationship between renal cell carcinoma and nuclear retinoid/rexinoid receptors. RESULTS: Use of retinoids/rexinoids in the treatment of locally advanced and metastatic RCC significantly prolongs median time of tumour progression and overall survival of patients. Combination therapy with other preparations has greater efficacy than treatment with retinoids alone. Patient survival can be predicted on the basis of the expression of different all-trans retinoic acid receptor (RAR) and 9-cis retinoic acid receptor (RXR) subtypes. CONCLUSIONS: Since nuclear retinoid receptors play a crucial role as ligand-activated, DNA binding, trans-acting, transcription-modulating proteins involved in a general molecular mechanism responsible for transcriptional responses in target genes, retinoids might be an alternative approach for the treatment of renal cell carcinoma.

• MeSH
• karcinom z renálních buněk etiologie   MeSH
• lidé MeSH
• nádory ledvin etiologie   MeSH
• receptory cytoplazmatické a nukleární fyziologie   MeSH
• receptory kyseliny retinové fyziologie   MeSH
• retinoidní X receptory fyziologie   MeSH
• rizikové faktory MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• receptory cytoplazmatické a nukleární MeSH
• receptory kyseliny retinové MeSH
• retinoidní X receptory MeSH

The main intention of this study was the investigation of impact of natural biologically active ligands of nuclear retinoid/retinoid X receptors (all-trans and 9-cis retinoic acid) on proteomic pattern in human estrogen receptor negative breast cancer cell line MDA-MB-231. For this purpose, proteomic strategies based on bottom-up method were applied. The total cell proteins were extracted utilizing a commercially Radio-Immunoprecipitation Assay (RIPA) buffer and separated on 2D sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE). The proteins were subsequently digested in-gel by trypsin and their characterization was achieved by MALDI-TOF/TOF. By employing PDQuest™ software, we identified more than 50 proteins affected by retinoic acid isomers. For more information, 9 proteins which are associated with tumor process were selected. We determined that derivatives of retinoic acid led to significantly reduced level of proteins belonging to metabolic pathway (e.g. glyceraldehyde-3-phosphate dehydrogenase or pyruvate kinase 2) or to other cellular processes as apoptosis, regulation of transcription process or epithelial-mesenchymal transition (e.g. annexins, nucleoside diphosphate kinase B, vimentin). On the other hand all-trans retinoic acid treatment indicates up-regulated effect for heterogeneous nuclear ribonucleoprotein A2/B1.

• Klíčová slova
• Biomarker, Breast cancer, MDA-MB-231, Proteomics, Retinoids,
• MeSH
• alitretinoin MeSH
• apoptóza účinky léků   MeSH
• elektroforéza v polyakrylamidovém gelu MeSH
• epitelo-mezenchymální tranzice účinky léků   MeSH
• heterogenní jaderné ribonukleoproteiny skupiny A-B genetika   metabolismus   MeSH
• lidé MeSH
• ligandy MeSH
• nádorové buněčné linie MeSH
• nádory prsu genetika   MeSH
• proteomika * MeSH
• protinádorové látky farmakologie   MeSH
• regulace genové exprese u nádorů * MeSH
• retinoidní X receptory genetika   metabolismus   MeSH
• tretinoin farmakologie   MeSH
• upregulace MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alitretinoin MeSH
• heterogenní jaderné ribonukleoproteiny skupiny A-B MeSH
• hnRNP A2 MeSH Prohlížeč
• ligandy MeSH
• protinádorové látky MeSH
• retinoidní X receptory MeSH
• tretinoin MeSH

An attempt has been made to delineate the role of natural and synthetic retinoid receptor ligands on vimentin expression in the human triple-negative breast cancer cells. The effects of currently synthesized triorganotin derivatives of the general formula R3SnX (R is butyl or phenyl, X is isothiocyanate), which are considered RXR ligands, were investigated in the human MDA-MB-231 breast cancer cell line. Studies were evaluated in the presence and absence of all-trans retinoic acid (ATRA), a natural RAR ligand. Vimentin represents the major protein associated with epithelial-mesenchymal transition (EMT), an essential process when the primary tumour transforms into a malignant one. mRNA and proteomic data obtained in this study, based on the PDQuest software protein evaluation and further quantification of proteins by iTRAQ analysis, suggest that vimentin was significantly reduced in the combination of RAR ligand and RXR ligand treatment. Both tested triorganotin compounds showed similarly reduced expression of vimentin, but tributyltin isothiocyanate (TBT-ITC) proved to be more effective than triphenyltin isothiocyanate (TPT-ITC). Furthermore, the effect of natural (9cRA) and synthetic RXR ligands, both chloride and isothiocyanate derivatives, on vimentin expression was compared.

• Klíčová slova
• Breast cancer, Proteomic, Triorganotin isothiocyanates, Vimentin, iTRAQ,
• MeSH
• 2D gelová elektroforéza MeSH
• down regulace MeSH
• epitelo-mezenchymální tranzice účinky léků   MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nádory prsu farmakoterapie   metabolismus   patologie   MeSH
• organocínové sloučeniny farmakologie   MeSH
• proteomika metody   MeSH
• protinádorové látky farmakologie   MeSH
• retinoidní X receptory agonisté   metabolismus   MeSH
• signální transdukce účinky léků   MeSH
• spektrometrie hmotnostní - ionizace laserem za účasti matrice MeSH
• tandemová hmotnostní spektrometrie MeSH
• tretinoin farmakologie   MeSH
• trialkylcínové sloučeniny farmakologie   MeSH
• vimentin metabolismus   MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• organocínové sloučeniny MeSH
• protinádorové látky MeSH
• retinoidní X receptory MeSH
• tretinoin MeSH
• trialkylcínové sloučeniny MeSH
• tributyltinisothiocyanate MeSH Prohlížeč
• triphenyltin MeSH Prohlížeč
• VIM protein, human MeSH Prohlížeč
• vimentin MeSH

Developmental exposure to environmental factors has been linked to obesity risk later in life. Nuclear receptors are molecular sensors that play critical roles during development and, as such, are prime candidates to explain the developmental programming of disease risk by environmental chemicals. We have previously characterized the obesogen tributyltin (TBT), which activates the nuclear receptors peroxisome proliferator-activated receptor γ (PPARγ) and retinoid X receptor (RXR) to increase adiposity in mice exposed in utero. Mesenchymal stem cells (MSCs) from these mice are biased toward the adipose lineage at the expense of the osteoblast lineage, and MSCs exposed to TBT in vitro are shunted toward the adipose fate in a PPARγ-dependent fashion. To address where in the adipogenic cascade TBT acts, we developed an in vitro commitment assay that permitted us to distinguish early commitment to the adipose lineage from subsequent differentiation. TBT and RXR activators (rexinoids) had potent effects in committing MSCs to the adipose lineage, whereas the strong PPARγ activator rosiglitazone was inactive. We show that activation of RXR is sufficient for adipogenic commitment and that rexinoids act through RXR to alter the transcriptome in a manner favoring adipogenic commitment. RXR activation alters expression of enhancer of zeste homolog 2 (EZH2) and modifies genome-wide histone 3 lysine 27 trimethylation (H3K27me3) in promoting adipose commitment and programming subsequent differentiation. These data offer insights into the roles of RXR and EZH2 in MSC lineage specification and shed light on how endocrine-disrupting chemicals such as TBT can reprogram stem cell fate.

• MeSH
• adipogeneze účinky léků   genetika   fyziologie   MeSH
• buněčná diferenciace účinky léků   genetika   MeSH
• chromatin účinky léků   fyziologie   MeSH
• endokrinní disruptory farmakologie   MeSH
• epigeneze genetická účinky léků   MeSH
• exprese genu účinky léků   MeSH
• EZH2 protein genetika   MeSH
• genový knockdown veterinární   MeSH
• mezenchymální kmenové buňky cytologie   MeSH
• myši inbrední C57BL MeSH
• myši MeSH
• obezita etiologie   MeSH
• PPAR gama fyziologie   MeSH
• retinoidní X receptory účinky léků   fyziologie   MeSH
• sekvenční analýza RNA veterinární   MeSH
• trialkylcínové sloučeniny farmakologie   MeSH
• tukové buňky cytologie   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• chromatin MeSH
• endokrinní disruptory MeSH
• Ezh2 protein, mouse MeSH Prohlížeč
• EZH2 protein MeSH
• PPAR gama MeSH
• retinoidní X receptory MeSH
• trialkylcínové sloučeniny MeSH
• tributyltin MeSH Prohlížeč

Some phytoplankton species were shown to produce teratogenic retinoids. This study assessed the variability in the extracellular production of compounds with retinoid-like activity for 50 independent cultivations of wide spectra of species including 12 cyanobacteria (15 strains) and 4 algae of different orders. Extracellular retinoid-like activity was detected for repeated cultivations of six cyanobacteria. The results were consistent for some species including Microcystis aeruginosa and Aphanizomenon gracile. The detected retinoid-like activities ranged from below the limit of quantification of 16 ng/L to over 6 µg all-trans retinoic acid (ATRA) equivalent/L. Nontargeted virtual fractionation together with suspect screening approach enabled to identify some retinoid-like compounds in exudates, including ATRA, 9/13-cis retinoic acid, all-trans 5,6-epoxy retinoic acid, 4keto-ATRA, 4keto-retinal, 4hydroxy-ATRA, and retinal. Most of them were for the first time repeatedly detected in exudates of all studied algae (at ng/L levels) and cyanobacteria. Their relative potencies ranged from 0.018 (retinal) to 1 compared to ATRA. They accounted for less than 0.1-50% of total detected retinoid-like activity. The high detected activities and concentrations of retinoids in some samples and their direct accessibility from exudates document potential risk of developmental toxicity for organisms in proximity of massive water blooms.

• Klíčová slova
• Cyanobacteria, Exudates, Retinoic acid receptor, Retinoid-like activity, Retinoids,
• MeSH
• Aphanizomenon * MeSH
• fytoplankton MeSH
• Microcystis * MeSH
• retinoidy MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• retinoidy MeSH

Sox3/SOX3 gene is considered to be one of the earliest neural markers in vertebrates. Despite the mounting evidence that Sox3/SOX3 is one of the key players in the development of the nervous system, limited data are available regarding the transcriptional regulation of its expression. This review is focused on the retinoic acid induced regulation of SOX3 gene expression, with particular emphasis on the involvement of retinoid receptors. Experiments with human embryonal carcinoma cells identified two response elements involved in retinoic acid/retinoid X receptor-dependent activation of the SOX3 gene expression: distal atypical retinoic acid-response element, consisting of two unique G-rich boxes separated by 49 bp, and proximal element comprising DR-3-like motif, composed of two imperfect hexameric half-sites. Importantly, the retinoic acid-induced SOX3 gene expression could be significantly down-regulated by a synthetic antagonist of retinoid receptors. This cell model provides a solid base for further studies on mechanism(s) underlying regulation of expression of SOX3 gene, which could improve the understanding of molecular signals that induce neurogenesis in the stem/progenitor cells both during development and in adulthood.

• MeSH
• lidé MeSH
• nádorové buněčné linie MeSH
• nervové kmenové buňky účinky léků   metabolismus   MeSH
• neurogeneze MeSH
• receptory kyseliny retinové účinky léků   metabolismus   MeSH
• responzivní elementy MeSH
• retinoidy farmakologie   MeSH
• signální transdukce MeSH
• transkripční faktory SOXB1 genetika   metabolismus   MeSH
• vazebná místa MeSH
• vývojová regulace genové exprese * účinky léků   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• receptory kyseliny retinové MeSH
• retinoidy MeSH
• SOX3 protein, human MeSH Prohlížeč
• transkripční faktory SOXB1 MeSH