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Retinoid X Receptor

Verena Hiebl, Angela Ladurner, Simone Latkolik, Verena M Dirsch
Nuclear receptors (NRs) represent attractive targets for the treatment of metabolic syndrome-related diseases. In addition, natural products are an interesting pool of potential ligands since they have been refined under evolutionary pressure to interact with proteins or other biological targets. This review aims to briefly summarize current basic knowledge regarding the liver X (LXR) and farnesoid X receptors (FXR) that form permissive heterodimers with retinoid X receptors (RXR). Natural product-based ligands for these receptors are summarized and the potential of LXR, FXR and RXR as targets in precision medicine is discussed...
March 13, 2018: Biotechnology Advances
Éverton L Vogt, Jorge F A Model, Anapaula S Vinagre
Organotins (OTs) are considered some of the most toxic chemicals introduced into aquatic environments by anthropogenic activities. They are widely used for agricultural and industrial purposes and as antifouling additives on boat hull's paints. Even though the use of OTs was banned in 2008, elevated levels of OTs can still be detected in aquatic environments. OTs' deleterious effects upon wildlife and experimental animals are well documented and include endocrine disruption, immunotoxicity, neurotoxicity, genotoxicity, and metabolic dysfunction...
2018: Frontiers in Endocrinology
Constance A Mitchell, Subham Dasgupta, Sharon Zhang, Heather M Stapleton, David C Volz
Triphenyl phosphate (TPHP) is an unsubstituted aryl phosphate ester used as a flame retardant and plasticizer within the United States. Using zebrafish as a model, the objectives of this study were to rely on 1) mRNA-sequencing to uncover pathways disrupted following embryonic TPHP exposure and 2) high-content screening to identify nuclear receptor ligands that enhance or mitigate TPHP-induced cardiotoxicity. Based on mRNA-sequencing, TPHP exposure from 24 to 72 h post fertilization (hpf) resulted in a concentration-dependent increase in the number of transcripts significantly affected at 72 hpf, and pathway analysis revealed that five out of nine nuclear receptor pathways were associated with the retinoid X receptor (RXR)...
February 24, 2018: Toxicological Sciences: An Official Journal of the Society of Toxicology
M Herian, M R Luck, M Grzesiak
Recently it has been shown that vitamin D(3) acting via its cognate receptor (VDR) regulates the growth, differentiation and function of female reproductive tissues including ovary. The aim of the study was to examine the effect of testosterone (T) and its antagonist 2-hydroxyflutamide (HF) on VDR protein expression and function in porcine ovarian follicles. Medium size antral follicles expressing great amount of androgen receptors and represent high steroidogenic activity were used in this research. After 6 h incubation of whole follicles with T, HF or T+HF, immunohistochemical analysis of VDR revealed its nuclear localization in granulosa and theca interna cells in control and experimental groups...
March 12, 2018: Physiological Research
Adam M Reitzel, Jason Macrander, Daniel Mane-Padros, Bin Fang, Frances M Sladek, Ann M Tarrant
Nuclear receptors are a superfamily of transcription factors restricted to animals. These transcription factors regulate a wide variety of genes with diverse roles in cellular homeostasis, development, and physiology. The origin and specificity of ligand binding within lineages of nuclear receptors (e.g., subfamilies) continues to be a focus of investigation geared toward understanding how the functions of these proteins were shaped over evolutionary history. Among early-diverging animal lineages, the retinoid X receptor (RXR) is first detected in the placozoan, Trichoplax adhaerens...
March 3, 2018: Journal of Steroid Biochemistry and Molecular Biology
A A Szczepańska, M Łupicka, B M Socha, A J Korzekwa
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors belonging to the superfamily of nuclear receptors. Three isoforms have been described: alpha (PPARα), delta (PPARδ), and gamma (PPARγ). PPARs heterodimerize with retinoid X receptors (RXRs: RXRα, RXRβ and RXRγ). PPAR activity can be modulated by several ligands, including arachidonic acid (AA) metabolites. The aims of the study were to determine the effect of AA metabolites (prostaglandin [PG]E2 , PGF2α , leukotriene [LT]B4 , and LTC4 ) on mRNA (real-time PCR) and protein expression (Western blotting) of PPARα, PPARδ, and PPARγ, and on mRNA expression of RXRα, RXRβ, and RXRγ, in bovine epithelial, stromal, and myometrial primary uterine cells and in bovine stromal cells with silenced PPAR genes (N=10)...
March 3, 2018: General and Comparative Endocrinology
Gabriel H Campolina-Silva, Bruna T Maria, Germán A B Mahecha, Cleida A Oliveira
BACKGROUND: Protective roles have been proposed for vitamin D in prostate cancer, which has the advanced age as the major risk factor. However, little is known about the expression of the vitamin D receptor (VDR) in the aging prostate and its association with the development of epithelial lesions that affect tissue homeostasis and may precede prostate tumors. METHODS: VDR expression in the prostatic complex of young adults to senile Wistar rats, a natural model to study age-related prostatic disorders, was evaluated by immunohistochemical, Western blotting, and image-assisted analyzes...
March 5, 2018: Prostate
Bence Daniel, Gergely Nagy, Attila Horvath, Zsolt Czimmerer, Ixchelt Cuaranta-Monroy, Szilard Poliska, Tristan T Hays, Sascha Sauer, Jean Francois-Deleuze, Laszlo Nagy
Retinoid X receptor (RXR) is an obligate heterodimeric partner of several nuclear receptors (NRs), and as such a central component of NR signaling regulating the immune and metabolic phenotype of macrophages. Importantly, the binding motifs of RXR heterodimers are enriched in the tissue-selective open chromatin regions of resident macrophages, suggesting roles in subtype specification. Recent genome-wide studies revealed that RXR binds to thousands of sites in the genome, but the mechanistic details how the cistrome is established and serves ligand-induced transcriptional activity remained elusive...
February 28, 2018: Nucleic Acids Research
Tali Shalom-Barak, Jaclyn Liersemann, Babak Memari, Lawrence Flechner, Caitlin Devor, Tiffany M Bernardo, Suyeon Kim, Nobuyuki Matsumoto, Scott L Friedman, Ronald M Evans, John H White, Yaacov Barak
The nuclear receptor Peroxisome proliferator-activated receptor γ (PPARγ) is an essential regulator of placental development. To gain deeper insights into placental PPARγ signaling, we dissected its regulation of the Muc1 promoter. We find that unlike prototypic target activation by heterodimeric receptors, which is either stimulated by or refractory to Retinoid X receptor (RXR) ligands (rexinoids), induction of Muc1 by liganded PPARγ requires RXRα, but is inhibited by rexinoids. We demonstrate that this inhibition is mediated by the activation function 2 (AF2) domain of RXRα and that Muc1 activation entails altered AF2 structures of both PPARγ and RXRα...
February 20, 2018: Molecular and Cellular Biology
Ding-Yu Lee, Tung-Lin Yang, Yi-Hsuan Huang, Chih-I Lee, Li-Jing Chen, Yu-Tsung Shih, Shu-Yi Wei, Wei-Li Wang, Chih-Cheng Wu, Jeng-Jiann Chiu
BACKGROUND AND AIMS: MicroRNA (miR)-10a is a shear-regulated miR with the lowest expression in vascular endothelial cells (ECs) in athero-susceptible regions with oscillatory shear stress (OS). The aim of this study is to elucidate the relationship between EC miR-10a and atherosclerosis and develop a hemodynamics-based strategy for atherosclerosis treatment. METHODS: A combination of in vitro flow system and in vivo experimental animals was used to examine the functional roles of EC miR-10a and its clinical applications in atherosclerosis...
February 8, 2018: Atherosclerosis
Daisuke Aibara, Kimihiko Matsusue, Soichi Takiguchi, Frank J Gonzalez, Shigeru Yamano
Fat-specific protein 27 (FSP27) is highly expressed in the fatty liver of genetically obese ob/ob mice and promotes hepatic triglyceride (TG) accumulation. The nuclear hormone receptor liver X receptor α (LXRα) also plays a critical role in the control of TG levels in the liver. The present study demonstrated transcriptional regulation of Fsp27a and Fsp27b genes by LXRα. Treatment with the LXR ligand T0901317 markedly increased Fsp27a and Fsp27b mRNAs in wild-type C57BL/6J and ob/ob mouse livers. A reporter assay indicated that two LXR-responsive elements (LXREs) are necessary for LXRα-dependent induction of Fsp27a and Fsp27b promoter activities...
February 15, 2018: Molecular and Cellular Endocrinology
Nilanjana Tewari, Sherif Awad, František Duška, Julian P Williams, Andrew Bennett, Ian A Macdonald, Dileep N Lobo
BACKGROUND & AIMS: The aims of this study were to identify whether differences in distribution of adipose tissue and skeletal muscle in obese and non-obese individuals contribute to the magnitude of the postoperative inflammatory response and insulin resistance, with and without preoperative treatment with carbohydrate drinks. METHODS: Thirty-two adults (16 obese/16 non-obese) undergoing elective major open abdominal surgery participated in this 2 × 2 factorial, randomised, double-blind, placebo-controlled study...
February 14, 2018: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
Mei Song, Yinyan Sun, Ji Tian, Wenhui He, Guangwei Xu, Zhiyi Jing, Wenhui Li
Multiple steps of the life cycle of Hepatitis B virus (HBV) are known to be coupled to hepatic metabolism. However the details of involvement of hepatic metabolic milieu in HBV infection remain incompletely understood. Hepatic lipid metabolism is controlled by a complicated transcription factors network centered by Retinoid X receptor alpha (RXRα). Here, we report that RXRα negatively regulates HBV infection at early stage in cell cultures. RXR specific agonist Bexarotene inhibits HBV in HepG2 cells expressing the sodium taurocholate cotransporting polypeptide (NTCP) (HepG2-NTCP), HepaRG cells and primary Tupaia hepatocytes (PTHs); Reducing RXRα expression significantly enhanced HBV infection in the cells...
February 7, 2018: Journal of Virology
Lixia Xie, Yucheng He, Xiaoqiao Zhou, Xiaowen Li, Xiue Jin, Xiliang Wang, Deshi Shi
1. Cytochrome P450, which is expressed in humans and other animals, is a superfamily of drug-metabolizing enzymes that plays important roles in the metabolism of endogenous and xenobiotic substrates via oxidation, peroxidation, and reduction. Of endogenous substrates, interleukin (IL)-6 is a crucial cytokine involved in inflammation in the liver. The present study aims to elucidate the mechanisms through which IL-6 modulates cytochrome P450 expression. 2. CYP2C33 expression was found to be increased in HepLi cells and primary porcine hepatocytes treated with IL-6 in a concentration-dependent manner...
February 12, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Jorge Viera-Vera, José E García-Arrarás
Retinoic acid receptors (RAR) and retinoid X receptors (RXR) are ligand-mediated transcription factors that synchronize intricate signaling networks in metazoans. Dimer formation between these two nuclear receptors mediates the recruitment of co-regulatory complexes coordinating the progression of signaling cascades during developmental and regenerative events. In the present study we identified and characterized the receptors for retinoic acid in the sea cucumber Holothuria glaberrima; a model system capable of regenerative organogenesis during adulthood...
February 6, 2018: Gene
Ladislav Novotny, Leyla Sharaf, Mohammed E Abdel-Hamid, Julius Brtko
Triorganotins belong to toxic components present predominantly in antifouling paints for marine vessels. Tributyltin/triphenyltin at pico- or nanomolar concentrations in sea water are known to induce an irreversible sexual abnormality in females of over 190 marine species, an "imposex" phenomenon - the superimposition of male genitalia on a female. Moreover, trialkyltins and triaryltins function as potent nuclear retinoid X receptors (RXR) agonists. In mammals, triorganotin compounds induce immunosuppressive, metabolic, reproductive or developmental effects...
January 2018: General Physiology and Biophysics
Valentina Pomatto, Erika Cottone, Paolo Cocci, Matteo Mozzicafreddo, Gilberto Mosconi, Erik Russel Nelson, Francesco Alessandro Palermo, Patrizia Bovolin
Recent studies suggest that exposure to some plasticizers, such as Bisphenol A (BPA), play a role in endocrine/metabolic dispruption and can affect lipid accumulation in adipocytes. Here, we investigated the adipogenic activity and nuclear receptor interactions of four plasticizers approved for the manufacturing of food-contact materials (FCMs) and currently considered safer alternatives. Differentiating 3T3-L1 mouse preadipocytes were exposed to scalar concentrations (0.01-25 μM) of DiNP (Di-iso-nonyl-phthalate), DiDP (Di-iso-decyl-phthalate), DEGDB (Diethylene glycol dibenzoate), or TMCP (Tri-m-cresyl phosphate)...
February 2, 2018: Journal of Steroid Biochemistry and Molecular Biology
Shigeharu Ueki, Junko Nishikawa, Mineyo Fukuchi, Yasunori Konno, Masahide Takeda, Yuki Moritoki, Junichi Chihara, Ayumi Omokawa, Tomoo Saga, Makoto Hirokawa
Active metabolites of vitamin A, retinoic acids (RAs), are known to play critical roles in mucosal immune responses and dramatically inhibit human eosinophil apoptosis, but the detailed mechanisms have not been elucidated. We previously screened for ICAM-1 (CD54) upregulation in RA-stimulated human eosinophils by gene microarray analysis. As ICAM-1 induction and activation were observed to have a role in maintenance of eosinophil survival, we tested the hypothesis that RAs prolong eosinophil survival through ICAM-1 outside-in signaling...
January 31, 2018: Immunology Letters
Mónica Morales, Pedro Martínez-Paz, Paloma Sánchez-Argüello, Gloria Morcillo, José Luis Martínez-Guitarte
Bisphenol A (BPA), a known endocrine disrupting chemical (EDC) that can mimic the action of oestrogens by interacting with hormone receptors, is potentially able to influence reproductive functions in vertebrates and invertebrates. The freshwater pulmonate Physa acuta is a sensitive organism to xenobiotics appropriate for aquatic toxicity testing in environmental studies. This study was conducted to explore the effects of BPA on the Gastropoda endocrine system. The effects following a range of exposure times (5-96h) to BPA in P...
January 31, 2018: Ecotoxicology and Environmental Safety
Hilda E Ghadieh, Harrison T Muturi, Lucia Russo, Christopher C Marino, Simona S Ghanem, Saja S Khuder, Julie C Hanna, Sukanta Jash, Vishwajeet Puri, Garrett Heinrich, Cara Gatto-Weis, Kevin Y Lee, Sonia M Najjar
Exenatide, a glucagon-like peptide-1 receptor agonist, induces insulin secretion. Its role in insulin clearance has not been adequately examined. Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) promotes hepatic insulin clearance to maintain insulin sensitivity. Feeding C57BL/6J mice a high-fat diet down-regulates hepatic Ceacam1 transcription to cause hyperinsulinemia, insulin resistance, and hepatic steatosis, as in Ceacam1 null mice (Cc1-/- ). Thus, we tested whether exenatide regulates Ceacam1 expression in high-fat diet-fed mice and whether this contributes to its insulin sensitizing effect...
January 2018: Hepatology Communications
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