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Retinoid X Receptor

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https://www.readbyqxmd.com/read/27890585/cadmium-in%C3%A2-vivo-exposure-alters-stress-response-and-endocrine-related-genes-in-the-freshwater-snail-physa-acuta-new-biomarker-genes-in-a-new-model-organism
#1
Pedro Martínez-Paz, Mónica Morales, Paloma Sánchez-Argüello, Gloria Morcillo, José Luis Martínez-Guitarte
The freshwater snail Physa acuta is a sensitive organism to xenobiotics that is appropriate for toxicity testing. Cadmium (Cd) is a heavy metal with known toxic effects on several organisms, which include endocrine disruption and activation of the cellular stress responses. There is scarce genomic information on P. acuta; hence, in this work, we identify several genes related to the hormonal system, the stress response and the detoxification system to evaluate the effects of Cd. The transcriptional activity of the endocrine-related genes oestrogen receptor (ER), oestrogen-related receptor (ERR), and retinoid X receptor (RXR), the heat shock proteins genes hsp70 and hsp90 and a metallothionein (MT) gene was analysed in P...
November 24, 2016: Environmental Pollution
https://www.readbyqxmd.com/read/27865806/ikaros-exploiting-and-targeting-the-hematopoietic-stem-cell-niche-in-b-progenitor-acute-lymphoblastic-leukemia
#2
REVIEW
Michelle L Churchman, Charles G Mullighan
Genetic alterations of IKZF1 encoding the lymphoid transcription factor IKAROS are a hallmark of high risk B-progenitor ALL such as BCR-ABL1 positive (Ph+) and Ph-like ALL, and are associated with poor outcome, even in the era of contemporary chemotherapy incorporating tyrosine kinase inhibitors in the treatment of Ph+ ALL. Recent experimental mouse modeling of B-progenitor ALL has shown that IKZF1 alterations have multiple effects, including arresting differentiating, skewing lineage of leukemia from myeloid to lymphoid, and in Ph+ leukemia, conferring resistance to TKI therapy without abrogating ABL1 inhibition...
November 16, 2016: Experimental Hematology
https://www.readbyqxmd.com/read/27852823/phosphorylation-of-human-retinoid-x-receptor-%C3%AE-at-serine-260-impairs-its-subcellular-localization-receptor-interaction-nuclear-mobility-and-1%C3%AE-25dihydroxyvitamin-d3-dependent-dna-binding-in-ras-transformed-keratinocytes
#3
Sylvester Jusu, John F Presley, Richard Kremer
Human retinoid X receptor alpha (hRXRα) plays a critical role in DNA binding and transcriptional activity through heterodimeric association with several members of the nuclear receptor superfamily including the human vitamin D receptor (hVDR). We previously showed that hRXRα phosphorylation at serine 260 through the Ras-Raf-Mitogen activated protein kinase extra-cellular signal regulated kinases 1 and 2 (MAP kinase ERK1/2) activation is responsible for resistance to the growth inhibitory effects of 1α, 25dihydroxyvitamin D3 (1α,25(OH)2D3), the biologically active metabolite of vitamin D3 To further investigate the mechanism of this resistance we studied intranuclear dynamics of hVDR and hRXRα tagged constructs in living cells together with endogenous and tagged protein in fixed cells...
November 16, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27849367/fetal-exposure-to-low-levels-of-the-plasticizer-dehp-predisposes-the-adult-male-adrenal-gland-for-endocrine-disruption
#4
S Lee, D B Martinez-Arguelles, E Campioli, V Papadopoulos
In utero exposure to endocrine disrupting chemicals (EDCs) may affect adult health. Di-(2-ethylhexyl) phthalate (DEHP) is an EDC widely used in the production of polyvinyl chloride products and an ubiquitous environmental contaminant. Previously, we used a rat model system to show that fetal exposure to DEHP decreased levels of major steroid hormones in adulthood and that environmentally-relevant levels of DEHP affected both gene expression and epigenomic loci that were affected by exposure to high levels. In the adrenal gland, we reported that the peroxisome proliferator-activated receptor (PPAR) and cholesterol biosynthesis pathways were sensitive targets of DEHP...
November 16, 2016: Endocrinology
https://www.readbyqxmd.com/read/27842487/molecular-interactions-of-bexarotene-a-retinoid-drug-and-alzheimer-s-a%C3%AE-peptide-a-docking-study
#5
Zeenat Mirza, Mohd Amin Beg
Alzheimer's disease (AD) pathogenesis is primarily hallmarked by the production and accumulation of amyloid beta (Aβ) peptide. Along with the understanding of the neurodegenerative disease progression and its pathophysiological mechanisms, development of anti-Aβ targeted effective therapeutics is essential for AD management. Numerous therapeutic approaches targeting the production, toxicity and removal of Aβ are being attempted worldwide. Prime need is to design inhibitors which can slow down the Aβ aggregation process in a physiological environment...
November 14, 2016: Current Alzheimer Research
https://www.readbyqxmd.com/read/27833522/histamine-h3-receptors-and-its-antagonism-as-a-novel-mechanism-for-antipsychotic-effect-a-current-preclinical-clinical-perspective
#6
REVIEW
Danish Mahmood
Histamine H3 receptors are present as autoreceptors on histaminergic neurons and as heteroreceptors on nonhistaminergic neurones. They control the release and synthesis of histamine and several other key neurotransmitters in the brain. H3 antagonism may be a novel approach to develop a new class of antipsychotic medications given the gathering evidence reporting therapeutic efficacy in several central nervous system disorders. Several medications such as cariprazine, lurasidone, LY214002, bexarotene, rasagiline, raloxifene, BL-1020 and ITI-070 are being developed to treat the negative symptoms and cognitive impairments of schizophrenia...
October 2016: International Journal of Health Sciences
https://www.readbyqxmd.com/read/27824486/novel-epigenetic-biomarkers-mediating-bisphenol-a-exposure-and-metabolic-phenotypes-in-female-mice
#7
Olivia S Anderson, Jung H Kim, Karen E Peterson, Brisa N Sanchez, Karilyn E Sant, Maureen A Sartor, Caren Weinhouse, Dana C Dolinoy
There is compelling evidence that epigenetic modifications link developmental environmental insults to adult disease susceptibility. Animal studies have associated perinatal bisphenol A (BPA) exposure to altered DNA methylation, but these studies are often limited to candidate gene and global non-loci specific approaches. Utilizing an epigenome-wide discovery platform, we elucidate epigenetic alterations in liver tissue from adult offspring (10 months) following perinatal BPA exposure at human physiologically relevant doses (50 ng, 50 μg, and 50 mg BPA/kg diet)...
November 8, 2016: Endocrinology
https://www.readbyqxmd.com/read/27821527/left-right-analysis-of-mammary-gland-development-in-retinoid-x-receptor-%C3%AE-mice
#8
Jacqulyne P Robichaux, John W Fuseler, Shrusti S Patel, Steven W Kubalak, Adam Hartstone-Rose, Ann F Ramsdell
Left-right (L-R) differences in mammographic parenchymal patterns are an early predictor of breast cancer risk; however, the basis for this asymmetry is unknown. Here, we use retinoid X receptor alpha heterozygous null (RXRα(+/-)) mice to propose a developmental origin: perturbation of coordinated anterior-posterior (A-P) and L-R axial body patterning. We hypothesized that by analogy to somitogenesis-in which retinoic acid (RA) attenuation causes anterior somite pairs to develop L-R asynchronously-that RA pathway perturbation would likewise result in asymmetric mammary development...
December 19, 2016: Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences
https://www.readbyqxmd.com/read/27810320/trc4-an-improved-triptolide-derivative-specifically-targets-to-truncated-form-of-retinoid-x-receptor-alpha-in-cancer-cells
#9
Pei-Yu Wang, Wen-Jun Zeng, Jie Liu, Yun-Long Wu, Yinghui Ma, Zhiping Zeng, Ji-Yan Pang, Xiao-Kun Zhang, Xiaomei Yan, Alice Sze Tsai Wong, Jin-Zhang Zeng
The nuclear retinoid X receptor-α (RXRα) plays critical roles in cell homeostasis and in many physiological processes mainly through its transcriptional function. However, an N-terminal truncated form of RXRα, tRXRα, was frequently described in various cancer cells and tumor tissues, thus representing a new promising drug target. We recently demonstrated that triptolide (TR01) could target to the oncogenic activity of tRXRα. To improve its tumor selectivity, we developed several TR01 derivatives by introducing different amine ester groups on C-14-hydroxyl site...
October 31, 2016: Biochemical Pharmacology
https://www.readbyqxmd.com/read/27787652/transcriptional-control-of-apoptotic-cell-clearance-by-macrophage-nuclear-receptors
#10
Tamás Röszer
Apoptotic cell clearance by macrophages is key for normal tissue development and homeostasis. Nuclear receptors, such as peroxisome proliferator activated receptors (PPARs), liver X receptor (LXR), retinoic acid receptor (RAR), retinoid X receptor (RXR) and glucocorticoid receptor (GR) orchestrate this vital process. The underlying mechanism involves the transcriptional control of key genes of apoptotic cell recognition and internalization, such as Cd36, Mertk, Axl, C1qa, Tgm2, Abca1. In addition, apoptotic cell uptake leads to M2 activation of macrophages, and this process is also controlled at the gene transcription level by nuclear receptors...
October 27, 2016: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/27777363/transcriptome-pathway-analysis-of-pathological-and-physiological-aldosterone-producing-human-tissues
#11
Junhua Zhou, Brian Lam, Sudeshna G Neogi, Giles S H Yeo, Elena A B Azizan, Morris J Brown
Primary aldosteronism is present in ≈10% of hypertensives. We previously performed a microarray assay on aldosterone-producing adenomas and their paired zona glomerulosa and fasciculata. Confirmation of top genes validated the study design and functional experiments of zona glomerulosa selective genes established the role of the encoded proteins in aldosterone regulation. In this study, we further analyzed our microarray data using AmiGO 2 for gene ontology enrichment and Ingenuity Pathway Analysis to identify potential biological processes and canonical pathways involved in pathological and physiological aldosterone regulation...
October 24, 2016: Hypertension
https://www.readbyqxmd.com/read/27770255/characterisation-of-vitamin-d-related-molecules-and-calcium-sensing-receptor-in-human-fallopian-tube-during-the-menstrual-cycle-and-in-ectopic-pregnancy
#12
Bassem Refaat, Jawwad Ahmad, Shakir Idris, Fadi Fayez Kamfar, Ahmed Mohamed Ashshi, Sarah Abdullah Batwa, Faizah Ahmed Malibary
This is a prospective observational study that measures the expression of vitamin D (VD) metabolising and signalling molecules and Ca(2+) sensing receptor (CaSR) in human Fallopian tube (FT) during the menstrual cycle and ectopic pregnancy (EP). Fresh FTs were obtained during total abdominal hysterectomy at the follicular (n = 16) and midluteal (n = 16) phases. Specimens from remote and implantation sites as well as trophoblastic tissues were also freshly collected from each FT with EP (n = 10)...
October 22, 2016: Cell and Tissue Research
https://www.readbyqxmd.com/read/27769911/calcium-induced-apoptosis-of-developing-cerebellar-granule-neurons-depends-causally-on-ngfi-b
#13
Lars Peter Engeset Austdal, Gro H Mathisen, Else Marit Løberg, Ragnhild E Paulsen
Immediate early gene nerve growth factor-induced clone B (NGFI-B), a nuclear receptor important for differentiation and apoptosis, is expressed in mice and rat cerebellum from an early stage of postnatal development. Following apoptotic stimuli NGFI-B translocates to mitochondria to initiate cell death processes. Controlled cell death is critical for correct cerebellar development. Immunohistochemical analysis of NGFI-B in sections of mice cerebella showed NGFI-B to be expressed in granule neurons in vivo at a time (P8-11) when apoptosis is known to occur...
October 18, 2016: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/27768859/4-hydroxyalkenal-activated-ppar%C3%AE-mediates-hormetic-interactions-in-diabetes
#14
Shlomo Sasson
Activated peroxisome proliferator-activated receptor-δ (PPARδ) induces the expression of genes encoding enzymes that metabolize fatty acids and carbohydrate. Attempts to identify cellular activators of PPARδ produced large lists of various fatty acids and their metabolic derivatives; however, there is no consensus on specific and selective binding interactions of natural ligands with PPARδ. Most models on binding interactions within the ligand binding domain (LBD) of PPARδ have been derived from analyses of PPARδ-LBD crystals formed with synthetic low molecular weight ligands...
October 18, 2016: Biochimie
https://www.readbyqxmd.com/read/27763563/cloning-and-expression-of-ecdysone-receptor-and-retinoid-x-receptor-from-procambarus-clarkii-induction-by-eyestalk-ablation
#15
Tian-Hao Dai, Ali Sserwadda, Kun Song, Ya-Nan Zang, Huai-Shun Shen
Ecdysone receptor and retinoid X receptor are key regulators in molting. Here, full length ecdysone receptor (PcEcR) and retinoid X receptor (PcRXR) cDNAs from Procambarus clarkii were cloned. Full length cDNA of PcEcR has 2500 bp, encoding 576 amino acid proteins, and full length cDNA of PcRXR has 2593 bp, in which a 15 bp and a 204 bp insert/deletion splice variant regions in DNA binding domain and hinge domain were identified. The two splice variant regions in PcRXR result four isoforms: PcRXR1-4, encoding 525, 520, 457 and 452 amino acids respectively...
October 18, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27734691/-endocrine-complications-of-modern-cancer-therapy
#16
Jan Čáp
Treatment with tyrosine kinase inhibitors leads to thyroid dysfunction in up to one half of treated patients, hypothyroidism being the most common. It is caused by destructive thyroiditis, impaired transport of T4 into the cell and deiodinase induction. Bexarotene is a nuclear retinoid X receptor agonist. Its application is accompanied with central hypothyroidism and hypertriglyceriaemia in virtually all patients and it also increases thyroxin metabolism. Autoimmune endocrine side effects are common in cancer immunotherapy...
2016: Vnitr̆ní Lékar̆ství
https://www.readbyqxmd.com/read/27729412/reduced-adiponectin-expression-after-high-fat-diet-is-associated-with-selective-up-regulation-of-aldh1a1-and-further-retinoic-acid-receptor-signaling-in-adipose-tissue
#17
Jean-Francois Landrier, Elnaz Kasiri, Esma Karkeni, Johanna Mihály, Gabriella Béke, Kathrin Weiss, Renata Lucas, Gamze Aydemir, Jérome Salles, Stéphane Walrand, Angel R de Lera, Ralph Rühl
Adiponectin is an adipocyte-derived adipokine with potent antidiabetic, anti-inflammatory, and antiatherogenic activity. Long-term, high-fat diet results in gain of body weight, adiposity, further inflammatory-based cardiovascular diseases, and reduced adiponectin secretion. Vitamin A derivatives/retinoids are involved in several of these processes, which mainly take place in white adipose tissue (WAT). In this study, we examined adiponectin expression as a function of high dietary fat and high vitamin A conditions in mice...
October 11, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27721113/a-vitamin-d-pathway-gene-gene-interaction-affects-low-density-lipoprotein-cholesterol-levels
#18
Nathália Grave, Luciana Tovo-Rodrigues, Janaína da Silveira, Diego Luiz Rovaris, Simone Morelo Dal Bosco, Verônica Contini, Júlia Pasqualini Genro
Much evidence suggests an association between vitamin D deficiency and chronic diseases such as obesity and dyslipidemia. Although genetic factors play an important role in the etiology of these diseases, only a few studies have investigated the relationship between vitamin D-related genes and anthropometric and lipid profiles. The aim of this study was to investigate the association of three vitamin D-related genes with anthropometric and lipid parameters in 542 adult individuals. We analyzed the rs2228570 polymorphism in the vitamin D receptor gene (VDR), rs2134095 in the retinoid X receptor gamma gene (RXRG) and rs7041 in the vitamin D-binding protein gene (GC)...
August 15, 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27714239/tetrazolone-as-an-acid-bioisostere-application-to-marketed-drugs-containing-a-carboxylic-acid
#19
Matthew A J Duncton, Ryan B Murray, Gary Park, Rajinder Singh
Matched molecular pair analysis was used to evaluate the ability of a tetrazolone group to act as a bioisostere of a carboxylic acid. Compound 7, a tetrazolone of the anti-hypertensive drug, telmisartan 6, was shown to be a potent AT1 antagonist (Kb = 0.14 nM), with activity comparable to telmisartan itself (Kb = 0.44 nM). Additionally, compound 9, a tetrazolone congener of the marketed anti-cancer agent, bexarotene 8, was shown to be an agonist at the retinoid X receptor alpha (EC50 = 64 nM). Compounds containing a tetrazolone group showed similar microsomal stability and plasma protein binding to marketed acid counterparts, while also reducing the value for clog P...
October 4, 2016: Organic & Biomolecular Chemistry
https://www.readbyqxmd.com/read/27698228/transcriptional-regulation-of-cyp2d6-expression
#20
Xian Pan, Miaoran Ning, Hyunyoung Jeong
CYP2D6-mediated drug metabolism exhibits large interindividual variability. While genetic variations in CYP2D6 gene are well-known contributors to the variability, accumulating data indicate that transcriptional regulation of CYP2D6 may also account for part of CYP2D6 variability. Yet, factors governing transcriptional regulation of CYP2D6 are poorly understood. Recently, mechanistic studies for increased CYP2D6-mediated drug metabolism in pregnancy revealed an important role of a transcription factor small heterodimer partner (SHP) as a transcriptional repressor of CYP2D6...
October 3, 2016: Drug Metabolism and Disposition: the Biological Fate of Chemicals
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