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Retinoic acid receptors

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https://www.readbyqxmd.com/read/28811909/a-fourth-subtype-of-retinoic-acid-receptor-related-orphan-receptors-is-activated-by-oxidized-all-trans-retinoic-acid-in-medaka-oryzias-latipes
#1
Kotowa Sakai, Haruka Fukushima, Yuya Yamamoto, Toshitaka Ikeuchi
BACKGROUND: The three known subtypes of the retinoic acid receptor-related orphan receptor (ROR) have been implicated in the control of immunity, brain function, and circadian rhythm in mammals. Here, we demonstrate by phylogenetic analysis that there were originally four subtypes of RORs in vertebrates. One of the novel ror paralogs, rord1 (rorca in the Ensembl database), is conserved among teleosts, but absent in mammals. Using medaka (Oryzias latipes) as a model teleost, we evaluated the expression pattern of this gene, its transactivational properties for endogenic chemicals, and its ability to activate the promoters of putative target genes...
2017: Zoological Letters
https://www.readbyqxmd.com/read/28802580/suppressive-role-of-ogt-mediated-o-glcnacylation-of-bap1-in-retinoic-acid-signaling
#2
Seungtae Moon, Yong-Kyu Lee, Sang-Wang Lee, Soo-Jong Um
BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). Here, we confirmed the physical interaction and investigated its functional significance. The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28802563/metabolic-circuit-involving-free-fatty-acids-microrna-122-and-triglyceride-synthesis-in-liver-and-muscle-tissues
#3
Chofit Chai, Mila Rivkin, Liav Berkovits, Alina Simerzin, Elina Zorde-Khvalevsky, Nofar Rosenberg, Shiri Klein, Dayana Yaish, Ronen Durst, Shoshana Shpitzen, Shiran Udi, Joseph Tam, Joerg Heeren, Anna Worthmann, Christoph Schramm, Johannes Kluwe, Revital Ravid, Eran Hornstein, Hilla Giladi, Eithan Galun
BACKGROUND & AIMS: Effective treatments are needed for hepatic steatosis characterized by accumulation of triglycerides in hepatocytes, which leads to hepatocellular carcinoma. MicroRNA 122 (MIR122) is expressed only in the liver, where it regulates lipid metabolism. We investigated the mechanism by which free fatty acids (FFAs) regulate MIR122 expression and the effect of MIR122 on triglyceride synthesis. METHODS: We analyzed MIR122 promoter activity and validated its target mRNAs by transfection of luciferase reporter plasmids into Huh7, BNL-1ME, and HEK293 cultured cell lines...
August 9, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28800395/using-chemistry-to-target-neuroblastoma
#4
Jeanne N Hansen, Xingguo Li, Y George Zheng, Louis T Lotta, Abhishek Dedhe, Nina F Schor
Neuroblastoma is a cancer of the neural crest almost exclusively seen in childhood. While children with single, small primary tumors are often cured with surgery alone, the 65% of children with neuroblastoma whose disease has metastasized have less than a 50% chance of surviving five years after diagnosis. Innovative pharmacological strategies are critically needed for these children. Efforts to identify novel targets that afford ablation of neuroblastoma with minimal toxicity to normal tissues are underway...
August 11, 2017: ACS Chemical Neuroscience
https://www.readbyqxmd.com/read/28794402/dec1-negatively-regulates-the-expression-of-cxcl10-and-ccl5-induced-by-poly-ic-in-normal-human-mesangial-cells
#5
Qiang Liu, Tadaatsu Imaizumi, Keishu Murakami, Hiroshi Tanaka, Yunyan Wu, Tadashi Yoshizawa, Satoko Morohashi, Hiroko Seino, Hiroshi Kijima
The functions of differentiated embryonic chondrocyte gene (DEC) 1, a basic helix-loop-helix (bHLH) transcription factor, have been reported to be associated with the regulation of mammalian circadian rhythms, differentiation of chondrocytes and skeletal muscles, apoptosis, hypoxia-induced reactions and epithelial mesenchymal transition. Our previous report showed that another bHLH transcription factor DEC2 constitutes a negative feedback loop in Toll-like receptor 3 (TLR3)/interferon (IFN)-β-mediated inflammatory responses in human mesangial cells...
2017: Biomedical Research
https://www.readbyqxmd.com/read/28783681/the-orphan-nuclear-receptor-ror%C3%AE-and-group-3-innate-lymphoid-cells-drive-fibrosis-in-a-mouse-model-of-crohn-s-disease
#6
Bernard C Lo, Matthew J Gold, Michael R Hughes, Frann Antignano, Yanet Valdez, Colby Zaph, Kenneth W Harder, Kelly M McNagny
Fibrosis is the result of dysregulated tissue regeneration and is characterized by excessive accumulation of matrix proteins that become detrimental to tissue function. In Crohn's disease, this manifests itself as recurrent gastrointestinal strictures for which there is no effective therapy beyond surgical intervention. Using a model of infection-induced chronic gut inflammation, we show that Rora-deficient mice are protected from fibrosis; infected intestinal tissues display diminished pathology, attenuated collagen deposition, and reduced fibroblast accumulation...
September 2, 2016: Science Immunology
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#7
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28776549/label-free-detection-for-a-dna-methylation-assay-using-raman-spectroscopy
#8
Jeongho Kim, Hae Jeong Park, Jae Hyung Kim, Boksoon Chang, Hun-Kuk Park
BACKGROUND: DNA methylation has been suggested as a biomarker for early cancer detection and treatment. Varieties of technologies for detecting DNA methylation have been developed, but they are not sufficiently sensitive for use in diagnostic devices. The aim of this study was to determine the suitability of Raman spectroscopy for label-free detection of methylated DNA. METHODS: The methylated promoter regions of cancer-related genes cadherin 1 (CDH1) and retinoic acid receptor beta (RARB) served as target DNA sequences...
August 20, 2017: Chinese Medical Journal
https://www.readbyqxmd.com/read/28774591/topical-ror-inverse-agonists-suppress-inflammation-in-mouse-models-of-atopic-dermatitis-and-acute-irritant-dermatitis
#9
Jun Dai, Min-Kyung Choo, Jin Mo Park, David E Fisher
The retinoic acid receptor-related orphan receptors RORα and RORγ are critical for the functions of specific subsets of T cells and innate lymphoid cells, which are key drivers of inflammatory disease in barrier tissues. Here, we investigate the anti-inflammatory potential of SR1001, a synthetic RORα/γ inverse agonist, in mouse models of atopic dermatitis and acute irritant dermatitis. Topical treatment with SR1001 reduces epidermal and dermal features of MC903-induced atopic dermatitis-like disease, and suppresses the production of type 2 cytokines and other inflammatory mediators in lesional skin...
July 31, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28766684/epigallocatechin-3-gallate-promotes-all-trans-retinoic-acid-induced-maturation-of-acute-promyelocytic-leukemia-cells-via-pten
#10
Shifei Yao, Liang Zhong, Min Chen, Yi Zhao, Lianwen Li, Lu Liu, Ting Xu, Chunlan Xiao, Liugen Gan, Zhiling Shan, Beizhong Liu
Acute promyelocytic leukemia (APL) is a distinctive subtype of acute myeloid leukemia (AML) in which the hybrid protein promyelocytic leukemia protein/retinoic acid receptor α (PML/RARα) acts as a transcriptional repressor impairing the expression of genes that are critical to myeloid cell mutation. We aimed at explaining the molecular mechanism of green tea polyphenol epigallocatechin-3-gallate (EGCG) enhancement of ATRA-induced APL cell line differentiation. Tumor suppressor phosphatase and tensin homolog (PTEN) was found downregulated in NB4 cells and rescued by proteases inhibitor MG132...
September 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28762092/socs1-and-pattern-recognition-receptors-tlr9-and-rig-i-novel-haplotype-associations-in-egyptian-fibrotic-cirrhotic-patients-with-hcv-genotype-4
#11
Samar S Youssef, Nadia M Hamdy
In this paper we explore the role of suppressor of cytokine signaling 1 (SOCS1) (rs243327), the regulator of toll-like receptor-9 (TLR9) (rs352140), retinoic acid inducible gene-I (RIG-I) (rs669260), and cluster of differentiation 152 (CD152) (rs231776) in fibrotic/cirrhotic patients. Single nucleotide polymorphisms (SNPs) within these genes as well as haplotype analyses were performed on a cohort of 120 Egyptian fibrotic patients. Fibrosis had progressed from HCV genotype 4 infections. Using RT-PCR, SNPs were evaluated in the DNA collected from each patient using TaqMan(®) genotyping assays...
July 31, 2017: Archives of Virology
https://www.readbyqxmd.com/read/28759951/promoter-hypermethylation-of-rar-%C3%AE-tumor-suppressor-gene-in-gastric-carcinoma-association-with-histological-type-and-clinical-outcomes
#12
Maedeh Mohsenzadeh, Rouhallah Najjar Sadeghi, Mohsen Vahedi, Fereshteh Kamani, Mehrdad Hashemi, Hamid Asadzadeh, Mohammad Reza Zali
BACKGROUND: While gastric cancer is a common cancer in the world and Iran, its molecular mechanisms are not fully understood as yet. Epigenetic modifications can lead to alteration of gene expression and development of tumorigenesis mechanisms. METHODS: To clarify the difference in DNA methylation pattern of histological types in gastric carcinoma, CpG islands in the promoters of retinoic acid receptor β gene (RAR-β) was studied using methylation-specific PCR...
July 19, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28757615/ror%C3%AE-controls-hepatic-lipid-homeostasis-via-negative-regulation-of-ppar%C3%AE-transcriptional-network
#13
Kyeongkyu Kim, Kyungjin Boo, Young Suk Yu, Se Kyu Oh, Hyunkyung Kim, Yoon Jeon, Jinhyuk Bhin, Daehee Hwang, Keun Il Kim, Jun-Su Lee, Seung-Soon Im, Seul Gi Yoon, Il Yong Kim, Je Kyung Seong, Ho Lee, Sungsoon Fang, Sung Hee Baek
The retinoic acid receptor-related orphan receptor-α (RORα) is an important regulator of various biological processes, including cerebellum development, circadian rhythm and cancer. Here, we show that hepatic RORα controls lipid homeostasis by negatively regulating transcriptional activity of peroxisome proliferators-activated receptor-γ (PPARγ) that mediates hepatic lipid metabolism. Liver-specific Rorα-deficient mice develop hepatic steatosis, obesity and insulin resistance when challenged with a high-fat diet (HFD)...
July 31, 2017: Nature Communications
https://www.readbyqxmd.com/read/28757363/poly-i-c-alleviates-obesity-related-pro-inflammatory-status-and-promotes-glucose-homeostasis
#14
Ying-Hui Wang, Yu-Gen Zhang
Obesity associated insulin resistance (IR) is implicated in chronic inflammation that mediated by the immune system. Imbalance between anti-inflammatory and pro-inflammatory response contributes to the origins and drivers of IR. However, cells of innate and adaptive immune system participate in the pathogenesis of IR, while glucose homeostasis related immune tolerance could be compromised high fat diet (HFD) reduced metabolic disorder. Although previous studies have demonstrated that anti-inflammatory therapy has a protective role in alleviating the pro-inflammatory status in HFD induced IR, the precise mechanism is still unclear...
July 27, 2017: Cytokine
https://www.readbyqxmd.com/read/28756872/retinoic-acid-improves-nephrotoxic-serum-induced-glomerulonephritis-through-activation-of-podocyte-retinoic-acid-receptor-%C3%AE
#15
Yan Dai, Anqun Chen, Ruijie Liu, Leyi Gu, Shuchita Sharma, Weijing Cai, Fadi Salem, David J Salant, Jeffrey W Pippin, Stuart J Shankland, Marcus J Moeller, Norbert B Ghyselinck, Xiaquiang Ding, Peter Y Chuang, Kyung Lee, John Cijiang He
Proliferation of glomerular epithelial cells, including podocytes, is a key histologic feature of crescentic glomerulonephritis. We previously found that retinoic acid (RA) inhibits proliferation and induces differentiation of podocytes by activating RA receptor-α (RARα) in a murine model of HIV-associated nephropathy. Here, we examined whether RA would similarly protect podocytes against nephrotoxic serum-induced crescentic glomerulonephritis and whether this effect was mediated by podocyte RARα. RA treatment markedly improved renal function and reduced the number of crescentic lesions in nephritic wild-type mice, while this protection was largely lost in mice with podocyte-specific ablation of Rara (Pod-Rara knockout)...
July 27, 2017: Kidney International
https://www.readbyqxmd.com/read/28746836/a-human-induced-pluripotent-stem-cell-based-in-vitro-assay-predicts-developmental-toxicity-through-a-retinoic-acid-receptor-mediated-pathway-for-a-series-of-related-retinoid-analogues
#16
Jessica A Palmer, Alan M Smith, Laura A Egnash, Michael R Colwell, Elizabeth L R Donley, Fred R Kirchner, Robert E Burrier
The relative developmental toxicity potency of a series of retinoid analogues was evaluated using a human induced pluripotent stem (iPS) cell assay that measures changes in the biomarkers ornithine and cystine. Analogue potency was predicted, based on the assay endpoint of the ornithine/cystine (o/c) ratio, to be all-trans-retinoic acid>TTNPB>13-cis-retinoic acid≈9-cis-retinoic acid>acitretin>etretinate>retinol. These rankings correlate with in vivo data and demonstrate successful application of the assay to rank a series of related toxic and non-toxic compounds...
July 23, 2017: Reproductive Toxicology
https://www.readbyqxmd.com/read/28744851/post-translational-regulation-of-antiviral-innate-signaling
#17
REVIEW
Yilong Zhou, Chenxi He, Wang Lin, Baoxue Ge
The innate immune system initiates immune responses by pattern-recognition receptors (PRR). Virus-derived nucleic acids are sensed by the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family and the toll-like receptor (TLR) family as well as the DNA sensor cyclic GMP-AMP (cGAMP) synthase (cGAS). These receptors activate IRF3/7 and NF-κB signaling pathways to induce the expression of type I interferons (IFNs) and other cytokines firing antiviral responses within the cell. However, to achieve a favorable outcome for the host, a balanced production of IFNs and activation of antiviral responses is required...
July 26, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28744254/metabolic-characterization-of-a-novel-ror%C3%AE-knockout-mouse-model-without-ataxia
#18
Cyrielle Billon, Sadichha Sitaula, Thomas P Burris
The retinoic acid receptor-related receptor α (RORα) is a nuclear receptor that plays an important role in regulation of metabolism and the immune system. Genetic deletion of the receptor yields mice with significant cerebellar developmental issues associated with severe ataxia. Although many metabolic studies have been performed in these models, the impaired locomotor activity of these mice is known to affect their normal mobility and feeding behaviors. This creates some difficulty in interpretation of the role of RORα in models of metabolic disease where feeding and muscle function is a critical component of the pathophysiology...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28743050/pml-rar%C3%AE-stabilized-by-zinc-in-human-acute-promyelocytic-leukemia-nb4-cells
#19
Bo Zhu, Jia-Yu Wang, Jun-Jie Zhou, Feng Zhou, Wei Cheng, Ying-Ting Liu, Jie Wang, Xiao Chen, Dian-Hua Chen, Lan Luo, Zi-Chun Hua
Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway...
July 19, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28741179/activation-of-liver-x-receptor-inhibits-oct2-mediated-organic-cation-transport-in-renal-proximal-tubular-cells
#20
Teerasak Wongwan, Suticha Kittayaruksakul, Nithi Asavapanumas, Varanuj Chatsudthipong, Sunhapas Soodvilai
Liver X receptor (LXR) is transcriptional factor that plays an important role in the regulation of energy metabolism such as cholesterol, lipid, and glucose metabolism as well as membrane transporters and channels. Using both in vitro and in vivo models, LXR regulation of the expression and function of renal organic cation transporter 2 (OCT2) was observed. Synthetic LXR agonist (GW3965) and endogenous LXR agonist (22R-hydroxycholesterol) significantly reduced the uptake of (3)H-MPP(+), a prototypic substrate of OCT2, in both OCT2- Chinese hamster ovary K1 and human renal proximal tubular cells (RPTEC/TERT1)...
July 25, 2017: Pflügers Archiv: European Journal of Physiology
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