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Retinoic acid receptors

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https://www.readbyqxmd.com/read/28724938/a-novel-role-for-rar%C3%AE-agonists-as-apolipoprotein-ciii-inhibitors-identified-from-high-throughput-screening
#1
Sang Jun Lee, Madhupriya Mahankali, Abdallah Bitar, Huafei Zou, Elizabeth Chao, Hung Nguyen, Jose Gonzalez, Dawna Caballero, Mitch Hull, Danling Wang, Peter G Schultz, Weijun Shen
Elevated triglyceride (TG) levels are well-correlated with the risk for cardiovascular disease (CVD). Apolipoprotein CIII (ApoC-III) is a key regulator of plasma TG levels through regulation of lipolysis and lipid synthesis. To identify novel regulators of TG levels, we carried out a high throughput screen (HTS) using an ApoC-III homogenous time resolved fluorescence (HTRF) assay. We identified several retinoic acid receptor (RAR) agonists that reduced secreted ApoC-III levels in human hepatic cell lines. The RARα specific agonist AM580 inhibited secreted ApoC-III by >80% in Hep3B cells with an EC50 ~2...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28718514/aldehyde-dehydrogenase-1-a1-regulates-energy-metabolism-in-adipocytes-from-different-species
#2
Kefeng Yang, Christopher Adin, Qiwen Shen, Ly James Lee, Lianbo Yu, Paolo Fadda, Arpad Samogyi, Kathleen Ham, Lu Xu, Chen Gilor, Ouliana Ziouzenkova
BACKGROUND: Survival and longevity of xenotransplants depend on immune function and ability to integrate energy metabolism between cells from different species. However, mechanisms for interspecies cross talk in energy metabolism are not well understood. White adipose tissue stores energy and is capable of mobilization and dissipation of energy as heat (thermogenesis) by adipocytes expressing uncoupling protein 1 (Ucp1). Both pathways are under the control of vitamin A metabolizing enzymes...
July 17, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28716760/properties-of-purified-cyp2r1-in-a-reconstituted-membrane-environment-and-its-25-hydroxylation-of-20-hydroxyvitamin-d3
#3
Chloe Y S Cheng, Tae-Kang Kim, Saowanee Jeayeng, Andrzej T Slominski, Robert C Tuckey
Recent studies indicate that CYP2R1 is the major 25-hydroxylase catalyzing the first step in vitamin D activation. Since the catalytic properties of CYP2R1 have been poorly studied to date and it is a membrane protein, we examined the purified enzyme in a membrane environment. CYP2R1 was expressed in E. coli and purified by nickel affinity- and hydrophobic interaction-chromatography and assayed in a reconstituted membrane system comprising phospholipid vesicles plus purified human NADPH-P450 oxidoreductase...
July 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28715808/retinoic-acid-facilitates-toll-like-receptor-4-expression-to-improve-intestinal-barrier-function-through-retinoic-acid-receptor-beta
#4
Yingying Li, Yuan Gao, Ting Cui, Ting Yang, Lan Liu, Tingyu Li, Jie Chen
BACKGROUND/AIMS: Vitamin A (VA) protects the intestinal epithelial barrier by improving cell migration and proliferation. Our previous studies demonstrated that VA deficiency (VAD) during pregnancy suppresses the systemic and mucosal immune responses in the intestines of offspring and that VA supplementation (VAS) during early life can increase immune cell counts. However, little is known about the mechanisms by which VA regulates intestinal epithelial barrier function. METHODS: Caco-2 cells were treated with all-trans retinoic acid (ATRA) for 24 hours to determine the optimum ATRA concentration to which the cells in question respond...
July 17, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28715585/retinoic-acid-engineered-amniotic-membrane-used-as-graft-or-homogenate-positive-effects-on-corneal-alkali-burns
#5
Romain Joubert, Estelle Daniel, Nicolas Bonnin, Aurélie Comptour, Christelle Gross, Corinne Belville, Frédéric Chiambaretta, Loïc Blanchon, Vincent Sapin
Purpose: Alkali burns are the most common, severe chemical ocular injuries, their functional prognosis depending on corneal wound healing efficiency. The purpose of our study was to compare the benefits of amniotic membrane (AM) grafts and homogenates for wound healing in the presence or absence of previous all-trans retinoic acid (atRA) treatment. Methods: Fifty male CD1 mice with reproducible corneal chemical burn were divided into five groups, as follows: group 1 was treated with saline solution; groups 2 and 3 received untreated AM grafts or grafts treated with atRA, respectively; and groups 4 and 5 received untreated AM homogenates or homogenates treated with atRA, respectively...
July 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28714877/alternative-pre-mrna-splicing-in-mammals-and-teleost-fish-a-effective-strategy-for-the-regulation-of-immune-responses-against-pathogen-infection
#6
REVIEW
Ming Xian Chang, Jie Zhang
Pre-mRNA splicing is the process by which introns are removed and the protein coding elements assembled into mature mRNAs. Alternative pre-mRNA splicing provides an important source of transcriptome and proteome complexity through selectively joining different coding elements to form mRNAs, which encode proteins with similar or distinct functions. In mammals, previous studies have shown the role of alternative splicing in regulating the function of the immune system, especially in the regulation of T-cell activation and function...
July 15, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28713967/involvement-of-notch2-in-all%C3%A2-trans-retinoic-acid%C3%A2-induced-inhibition-of-mouse-embryonic-palate-mesenchymal-cell-proliferation
#7
Yadong Zhang, Shiyi Dong, Jianning Wang, Miao Wang, Mu Chen, Hongzhang Huang
Cleft palate is among the most common congenital disorders, and can be induced by exposure to all‑trans retinoic acid (atRA) during mice and human embryogenesis. However, the mechanism underlying the implication of atRA in the development of cleft palate has yet to be elucidated. In the present study, atRA administered by gavage resulted in formation of a cleft palate in 99% of treated C57BL/6 mice. Notch2 was revealed to be upregulated in mouse embryonic palate mesenchymal (MEPM) cells in the atRA‑treated group compared with untreated control mice between embryonic day (E)12...
July 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28710430/rlr-mediated-antiviral-innate-immunity-requires-oxidative-phosphorylation-activity
#8
Takuma Yoshizumi, Hiromi Imamura, Tomohiro Taku, Takahiro Kuroki, Atsushi Kawaguchi, Kaori Ishikawa, Kazuto Nakada, Takumi Koshiba
Mitochondria act as a platform for antiviral innate immunity, and the immune system depends on activation of the retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) signaling pathway via an adaptor molecule, mitochondrial antiviral signaling. We report that RLR-mediated antiviral innate immunity requires oxidative phosphorylation (OXPHOS) activity, a prominent physiologic function of mitochondria. Cells lacking mitochondrial DNA or mutant cells with respiratory defects exhibited severely impaired virus-induced induction of interferons and proinflammatory cytokines...
July 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28705713/sn003-a-crf1-receptor-antagonist-attenuates-depressive-like-behavior-and-detrusor-overactivity-symptoms-induced-by-13-cis-retinoic-acid-in-rats
#9
Andrzej Wróbel, Urszula Doboszewska, Ewa Rechberger, Piotr Wlaź, Tomasz Rechberger
Overactive bladder (OAB) often co-exists with depression in women. The corticotropin-releasing factor (CRF) system participates in the pathophysiology of both disorders. Therefore, we tested the effects of acute treatment with a reversible CRF receptor type-1 (CRF1) antagonist, SN003 (1mg/kg, i.v.), representatives of first (solifenacin, 0.03mg/kg, i.v.) and second (mirabegron, 1mg/kg, i.v.) line treatments for OAB as well as an antidepressant imipramine (30mg/kg, i.p.) on changes in behavior and detrusor overactivity (DO) symptoms induced by a 6-week administration of 13-cis-retinoic acid (13-cis-RA, 1mg/kg/day, i...
July 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28705469/systematic-prioritization-of-functional-hotspot-in-rig-1-domains-using-pattern-based-conventional-molecular-dynamic-simulation
#10
P Raghuraman, R Jesu Jaya Sudan, J Lesitha Jeeva Kumari, C Sudandiradoss
BACKGROUND: Retinoic acid inducible gene 1 (RIG-1), multi-domain protein has a role-play in detecting viral nucleic acids and stimulates the antiviral response. Dysfunction of this protein due to mutations makes the route vulnerable to viral diseases. AIM: Identification of functional hotspots that maintains conformational stability in RIG-1 domains. METHODS: In this study, we employed a systematic in silico strategy on RIG-1 protein to understand the mechanism of structural changes upon mutation...
July 10, 2017: Life Sciences
https://www.readbyqxmd.com/read/28698385/retinoic-acid-receptor-related-orphan-receptor-alpha-stimulates-adipose-tissue-inflammation-by-modulating-endoplasmic-reticulum-stress
#11
Yin Liu, Yulong Chen, Jinlong Zhang, Yulan Liu, Yanjie Zhang, Zhiguang Su
Adipose tissue inflammation has been linked to metabolic diseases such as obesity and type 2 diabetes. However, the molecules that mediate inflammation in adipose tissue have not been addressed. Although retinoic acid receptor-related orphan receptor alpha (RORα) is known to be involved in the regulation of inflammatory response in some tissues, its role is largely unknown in adipose tissue. Conversely, it is known that endoplasmic reticulum (ER) stress and unfolding protein response (UPR) signaling affect the inflammatory response in obese adipose tissue, but whether RORα regulates these processes remains unknown...
July 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28698144/inhibiting-glycogen-synthase-kinase-3-and-transforming-growth-factor-%C3%AE-signaling-to-promote-epithelial-transition-of-human-adipose-mesenchymal-stem-cells
#12
Melina Setiawan, Xiao-Wei Tan, Tze-Wei Goh, Gary Hin-Fai Yam, Jodhbir S Mehta
BACKGROUND: This study was aimed to investigate the epithelial differentiation of human adipose-derived mesenchymal stem cells (ADSCs) by inhibiting glycogen synthase kinase-3 (GSK3) and transforming growth factor β (TGFβ) signaling. METHODS AND RESULTS: STEMPRO human ADSCs at passage 2 were treated with CHIR99021 (GSK3 inhibitor), E-616452 (TGFβ1 receptor kinase inhibitor), A-83-01 (TGFβ type 1 receptor inhibitor), valproic acid (histone deacetylase inhibitor), tranylcypromine (monoamine oxidase inhibitor) and all-trans retinoic acid for 72 h...
July 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28696254/human-monocyte-subsets-are-transcriptionally-and-functionally-altered-in-aging-in-response-to-pattern-recognition-receptor-agonists
#13
Talibah U Metcalf, Peter A Wilkinson, Mark J Cameron, Khader Ghneim, Cindy Chiang, Anne M Wertheimer, John B Hiscott, Janko Nikolich-Zugich, Elias K Haddad
Age-related alterations in immunity have been linked to increased incidence of infections and decreased responses to vaccines in the aging population. Human peripheral blood monocytes are known to promote Ag presentation and antiviral activities; however, the impact of aging on monocyte functions remains an open question. We present an in-depth global analysis examining the impact of aging on classical (CD14(+)CD16(-)), intermediate (CD14(+)CD16(+)), and nonclassical (CD14(dim)CD16(+)) monocytes. Monocytes sorted from nonfrail healthy adults (21-40 y) and old (≥65 y) individuals were analyzed after stimulation with TLR4, TLR7/8, and retinoic acid-inducible gene I agonists...
July 10, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28694088/enhanced-expression-of-tumour-suppressor-rar-%C3%AE-by-dspc-nano-formulated-lipo-atra-in-the-lung-of-b16f10-cell-implanted-c57bl6-mice-and-in-a549-cells
#14
V M Berlin Grace, Reshma Mahima Reji, Viswanathan Sundaram
AIM: All Trans Retinoic acid (ATRA) is an efficient drug for leukemia, but is not efficient therapy for solid cancers. Hence we have used 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC) and cholesterol lipo-ATRA to investigate its molecular therapeutic effect on lung cancer. The objective was to find whether it could enhance ATRA receptor, RAR-β expression in lung cells as it was lost in majority of cancers including lung cancer. MATERIALS AND METHODS: The study was made in an experimental C57BL/6 mice model developed by tail vein injection of B16F10 cells and in A549 human lung cancer cells...
July 7, 2017: Life Sciences
https://www.readbyqxmd.com/read/28692932/axon-guidance-pathways-served-as-common-targets-for-human-speech-language-evolution-and-related-disorders
#15
Huimeng Lei, Zhangming Yan, Xiaohong Sun, Yue Zhang, Jianhong Wang, Caihong Ma, Qunyuan Xu, Rui Wang, Erich D Jarvis, Zhirong Sun
Human and several nonhuman species share the rare ability of modifying acoustic and/or syntactic features of sounds produced, i.e. vocal learning, which is the important neurobiological and behavioral substrate of human speech/language. This convergent trait was suggested to be associated with significant genomic convergence and best manifested at the ROBO-SLIT axon guidance pathway. Here we verified the significance of such genomic convergence and assessed its functional relevance to human speech/language using human genetic variation data...
July 7, 2017: Brain and Language
https://www.readbyqxmd.com/read/28692043/cross-talk-between-progesterone-receptors-and-retinoic-acid-receptors-in-regulation-of-cytokeratin-5-positive-breast-cancer-cells
#16
L M Fettig, O McGinn, J Finlay-Schultz, D V LaBarbera, S K Nordeen, C A Sartorius
Half of estrogen receptor-positive breast cancers contain a subpopulation of cytokeratin 5 (CK5)-expressing cells that are therapy resistant and exhibit increased cancer stem cell (CSC) properties. We and others have demonstrated that progesterone (P4) increases CK5+ breast cancer cells. We previously discovered that retinoids block P4 induction of CK5+ cells. Here we investigated the mechanisms by which progesterone receptors (PR) and retinoic acid receptors (RAR) regulate CK5 expression and breast CSC activity...
July 10, 2017: Oncogene
https://www.readbyqxmd.com/read/28689802/comparison-of-phenotypic-and-global-gene-expression-changes-in-xenopus-tropicalis-embryos-induced-by-agonists-of-rar-and-rxr
#17
Jingmin Zhu, Lingling Hu, Lingyun Li, Xiao Huang, Huahong Shi
Retinoic acid functions through two classes of receptors, i.e., the retinoic acid receptor (RAR) and the retinoid X receptor (RXR). The difference in the role between RAR and RXR, however, are not well clarified. In the present study, we comparatively investigated the phenotypic and global gene expression changes in Xenopus tropicalis embryos induced by three different agonists, including a RAR selective ligand (all-trans retinoic acid, at-RA), a RXR selective ligand (fluorobexarotene, FBA) and their common ligand (9-cis retinoic acid, 9c-RA)...
July 6, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28687976/annexin-a2-s100a10-heterotetramer-is-upregulated-by-pml-rar%C3%AE-fusion-protein-and-promotes-plasminogen-dependent-fibrinolysis-and-matrix-invasion-in-acute-promyelocytic-leukemia
#18
Dan Huang, Yan Yang, Jian Sun, Xiaorong Dong, Jiao Wang, Hongchen Liu, Chengquan Lu, Xueyu Chen, Jing Shao, Jinsong Yan
Aberrant expression of annexin A2-S100A10 heterotetramer (AIIt) associated with PML/RARα fusion protein causes lethal hyperfibrinolysis in acute promyelocytic leukemia (APL), but the mechanism is unclear. To facilitate the investigation of regulatory association between ANXA2 and promyelocytic leukemia/retinoic acid receptor α (PML/RARα) fusion protein, this work was performed to determine the transcription start site of ANXA2 promoter with rapid amplification of 5'-cDNA ends analysis. Zinc-induced U937/PR9 cells expressed PML/RARα fusion protein, and resultant increases in ANXA2 transcripts and translational expressions of both ANXA2 and S100A10, while S100A10 transcripts remained constitutive...
July 8, 2017: Frontiers of Medicine
https://www.readbyqxmd.com/read/28687611/vitamin-a-regulates-akt-signaling-through-the-phospholipid-fatty-acid-composition
#19
Helmut Pein, Solveigh C Koeberle, Maria Voelkel, Freya Schneider, Antonietta Rossi, Maria Thürmer, Konstantin Loeser, Lidia Sautebin, Helen Morrison, Oliver Werz, Andreas Koeberle
Protein kinases, including the serine/threonine kinase Akt, mediate manifold bioactivities of vitamin A, although the mechanisms behind the sustained kinase activation are diffuse. To investigate the role of cellular lipids as targetable factors in Akt signaling, we combined mass spectrometry-based lipidomics with immunologic detection of Akt (Ser473) phosphorylation. A screening campaign revealed retinol (vitamin A alcohol) and all-trans retinoic acid (vitamin A acid) (RA) as hits that time-dependently (≥24 h) deplete phosphatidylcholine-bound polyunsaturated fatty acids (PUFA-PCs) from NIH-3T3 mouse fibroblasts while inducing Akt activation (EC50 ≈ 0...
July 7, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28685056/pml-silencing-inhibits-cell-proliferation-and-induces-dna-damage-in-cultured-ovarian-cancer-cells
#20
Sheng-Bing Liu, Zhong-Fei Shen, Yan-Jun Guo, Li-Xian Cao, Ying Xu
The promyelocytic leukemia (PML) gene is a tumor suppressor gene. It was first identified in acute promyelocytic leukemia, in which it is fused to retinoic acid receptor α by the (15;17) chromosomal translocation. The function of the PML protein is frequently lost or aberrant in human solid tumors. In human ovarian carcinoma tissue, PML detected by immunohistochemistry was highly expressed. A PML-silencing vector, pSRG-shPml, was constructed and used to transfect human ovarian cancer cells. Cells were cultured and selected with puromycin for 10-15 days, and then the PML mRNA expression levels were detected by RT-qPCR and immunofluorescence...
July 2017: Biomedical Reports
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