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Vitamin d signaling

Veijo Nurminen, Antonio Neme, Sabine Seuter, Carsten Carlberg
The myeloid master regulator CCAAT enhancer-binding protein alpha (CEBPA) is known as a pioneer factor. In this study, we report the CEBPA cistrome of THP-1 human monocytes after stimulation with the vitamin D receptor (VDR) ligand 1α,25-dihydroxyvitamin D3 (1,25(OH)2 D3 ) for 2, 8 and 24 h. About a third of the genomic VDR binding sites co-located with those of CEBPA. In parallel, the binding strength of 5% of the CEBPA cistrome, i.e. some 1500 sites, is significantly (p < 0.001) affected by 1,25(OH)2 D3 ...
December 11, 2018: Biochimica et biophysica acta. Gene regulatory mechanisms
Qian Li, Daming Chen, Qiwang Xiang, John Nicholas
Human herpesvirus 8 (HHV-8) viral interleukin-6 (vIL-6) localizes largely to the endoplasmic reticulum (ER) and here associates functionally with both the gp130 signal transducer and the novel ER membrane protein vitamin K epoxide reductase complex subunit 1 variant-2 (VKORC1v2). The latter interaction contributes to the viability of latently infected primary effusion lymphoma (PEL) cells and to HHV-8 productive replication, in part via promotion of ER-associated degradation (ERAD) of nascent pro-cathepsin D (pCatD) and consequent suppression of lysosome-localized pro-apoptotic mature CatD...
December 12, 2018: Journal of Virology
Kholghi Oskooei Vahid, Ghafouri-Fard Soudeh, Omrani Mir Davood
BACKGROUND: Long non-coding RNAs (lncRNAs) as an important fraction of human transcriptome have been shown to exert fundamental role in regulation of signaling pathways implicated in carcinogenesis. Among them is vitamin D receptor (VDR) signaling whose participation in various cancers including breast cancer (BC) is evident. In spite of the presence of several evidences for participation of lncRNAs as well as VDR signaling in BC pathogenesis, no comprehensive study has evaluated the link between lncRNA dysregulation and VDR signaling in BC...
2018: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
Yanfang Guo, Ling Zhu, Yi Ge, Hao Zhang
BACKGROUND: Vitamin D, a fat-soluble secosteroid, plays a key role in several metabolic diseases like diabetes. Diabetes is becoming a third leading chronic disease in the world, which seriously threatens human health. METHODS: In current study, we found the beneficial effects of vitamin D supplementation in obesity-related diabetes rat. Enzyme-linked immunosorbent assay, biochemical testing, real-time PCR and western blot were carried to investigate the effect of vitamin D supplementation on diabetes...
December 7, 2018: Minerva Endocrinologica
Matan Nachliely, Aviram Trachtenberg, Boris Khalfin, Karen Nalbandyan, Merav Cohen-Lahav, Kaori Yasuda, Toshiyuki Sakaki, Andrzej Kutner, Michael Danilenko
Acute myeloid leukemia (AML) is one of the deadliest hematological malignancies without effective treatment for most patients. Vitamin D derivatives (VDDs) - active metabolites 1α,25-dihydroxyvitamin D2 (1,25D2) and 1α,25-dihydroxyvitamin D3 (1,25D3) and their analogs - are differentiation-inducing agents which have potential for the therapy of AML. However, calcemic toxicity of VDDs limits their clinical use at doses effective against cancer cells in vivo. Here, we demonstrate that in AML cell cultures, moderate pro-differentiation effects of low concentrations of VDDs can be synergistically enhanced by structurally distinct compounds known to activate the transcription factor Nuclear Factor (Erythroid-derived 2)-Like 2 (NFE2L2 or Nrf2)...
November 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
X Wang, M Nachliely, J S Harrison, M Danilenko, G P Studzinski
Standard therapy for Acute Myeloid Leukemia (AML) is rarely curative, and several suggested improvements have had little success so far. We have reported that in an in vitro model of a potential therapeutic regimen for AML, the activity of cytarabine (AraC) is enhanced by a sequential treatment with a combination of the vitamin D2 analog Doxercalciferol (D2) and the plant-derived antioxidant carnosic acid (CA) Importantly, the enhancement occurred selectively in patient-derived AML blasts, but not in the normal bone marrow cells...
November 30, 2018: Journal of Steroid Biochemistry and Molecular Biology
Florian Lang, Christina Leibrock, Aleksandra A Pandyra, Christos Stournaras, Carsten A Wagner, Michael Föller
Fibroblast growth factor 23 (FGF23) is released primarily from osteoblasts/osteocytes in bone. In cooperation with the transmembrane protein Klotho, FGF23 is a powerful inhibitor of 1α 25OH Vitamin D Hydroxylase (Cyp27b1) and thus of the formation of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). As 1,25(OH)2D3 up-regulates intestinal calcium and phosphate absorption, the downregulation of 1,25(OH)2D3 synthesis counteracts phosphate excess and tissue calcification. FGF23 also directly inhibits renal phosphate reabsorption...
November 30, 2018: Kidney & Blood Pressure Research
Jing Xu, Maralee S Lawson, Fuhua Xu, Yongrui Du, Olena Y Tkachenko, Cecily V Bishop, Lucas Pejovic-Nezhat, David B Seifer, Jon D Hennebold
There is an increasing recognition that vitamin D plays important roles in female reproduction. Recent studies demonstrated that 1α,25-dihydroxyvitamin D3 (VD3), the biologically active form of vitamin D, improved ovarian follicle survival and growth in vitro . Therefore, we investigated the direct effects of VD3 at the specific preantral and antral stages of follicular development, and tested the hypothesis that vitamin D receptor (VDR) and enzymes critical for vitamin D biosynthesis are expressed in the primate ovary...
2018: Frontiers in Physiology
T Willinger
Cholesterol is an essential molecule for life. It is a component of the cell membrane, and it is a precursor molecule for bile acids, vitamin D and steroid hormones. Cholesterol is actively metabolized, but the impact of endogenous cholesterol metabolites on immune function, especially in the intestine, is poorly understood. In this review, I focus on oxysterols, hydroxylated forms of cholesterol, and their specialized functions in intestinal immunity. Oxysterols act through various intracellular and extracellular receptors and serve as key metabolic signals, coordinating immune activity and inflammation...
November 26, 2018: Journal of Internal Medicine
Q Li, Y Jia, W R Burris, P J Bridges, J C Matthews
The goal of this study was to test the hypothesis that sodium selenite (ISe), SEL-PLEX (OSe), vs. a 1:1 blend (MIX) of ISe and OSe in a basal vitamin-mineral (VM) mix would differentially alter pituitary transcriptome profiles in growing beef steers grazing an endophyte-infected tall fescue (E+) pasture. Predominately-Angus steers (BW = 183 ± 34 kg) were randomly selected from fall-calving cows grazing E+ pasture and consuming VM mixes that contained 35 ppm Se as ISe, OSe, or MIX forms. Steers were weaned, depleted of Se for 98 d, and subjected to summer-long common grazing of a 10...
November 22, 2018: Journal of Animal Science
Chad A Maschinot, Lianne Q Chau, Robert J Wechsler-Reya, M Kyle Hadden
The Hedgehog (Hh) pathway is a developmental pathway with therapeutic potential as a target for a variety of cancers. In recent years, several vitamin D-based compounds have been identified as potent inhibitors of Hh signaling. These analogues contain aromatic phenol A-ring mimics coupled to the CD-ring side chain of vitamin D3 through modified seco-B regions. To continue structure-activity relationship studies on this class of Hh pathway inhibitors, multiple series of vitamin D-based analogues that contain an amine-based seco-B tether and/or incorporate a hydroxyl moiety on C-25 were designed and synthesized...
November 10, 2018: European Journal of Medicinal Chemistry
X-J Lei, Y-L Xu, Y-Q Yang, Y-W Bing, Y-X Zhao
OBJECTIVE: To explore the protective role of Vitamin D Receptor (VDR) in retinal ganglion cells (RGCs) after high-level glucose induction, and to investigate its underlying mechanism. MATERIALS AND METHODS: Primary RGCs were isolated from 24-hour-old Sprague Dawley (SD) rats and cultured in 50 mmol/L glucose. The expression of VDR in RGCs induced by 50 mmol/L glucose at different time points was determined by Real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot, respectively...
November 2018: European Review for Medical and Pharmacological Sciences
Chiara Ricca, Alessia Aillon, Marta Viano, Loredana Bergandi, Elisabetta Aldieri, Francesca Silvagno
Vitamin D and TGF-β exert opposite effects on epithelial-mesenchymal EMT transition. Here we report a novel mechanism of action of TGF-β that promotes the counteracting activity of vitamin D; in two models of human epithelial-mesenchymal EMT transition we demonstrated for the first time that TGF-β strongly induced the expression of vitamin D receptor (VDR) and that 1,25(OH)2 D3 was able to contrast the TGF-β-driven EMT transition by transcriptional modulation. In human bronchial epithelial cells the effects of TGF-β on EMT transition markers (E-Cadherin expression and cell motility) were reversed by pre-treatment and co-treatment with 1,25(OH)2 D3, but not when the hormone was given later...
November 19, 2018: Journal of Steroid Biochemistry and Molecular Biology
Chenyue Liu, Ruyuan Zhu, Haixia Liu, Lin Li, Beibei Chen, Qiangqiang Jia, Lili Wang, Rufeng Ma, Simin Tian, Min Wang, Min Fu, Jianzhao Niu, Alexander N Orekhov, Sihua Gao, Dongwei Zhang, Baosheng Zhao
Purpose: The present study is aimed to explore whether the aqueous extract of Mori Folium (MF) exhibits bone protective effect by regulating calcium and redox homeostasis in diabetic rats, and to identify the signaling pathways involved in this process. Methods: Diabetic rats were established using high-sugar and high-fat diet and streptozotocin (STZ) (30 mg/kg for 3 consecutive days). The serum levels of osteocalcin (OC), insulin-like growth factor-1 (IGF-1), tartrate-resistant acid phosphatase (TRAP), phosphorus (P), calcium (Ca), 1,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ], parathormone (PTH), advanced glycation end products (AGEs), superoxide dismutase (SOD), and malondialdehyde (MDA), total antioxidant capacity (TAC), 8-hydroxy-2'-deoxyguanosine (8-OH-dG), and interleukin 6 (IL-6) were determined by ELISA or biochemical assays...
2018: Frontiers in Pharmacology
Kristine C Olson, Paige M Kulling Larkin, Rossana Signorelli, Cait E Hamele, Thomas L Olson, Mark R Conaway, David J Feith, Thomas P Loughran
Calcitriol, the active form of vitamin D, has been well documented to act directly on immune cells and malignant cells. Activated T cells are one of the best characterized targets of calcitriol, with effects including decreasing inflammatory cytokine output and promoting anti-inflammatory cytokine production. However, the effects of calcitriol on natural killer (NK) cells are less clear. Reports suggest that only immature NK cell populations are affected by calcitriol treatment resulting in impaired cytotoxic function and cytokine production, while mature NK cells may have little or no response...
November 16, 2018: Cytokine
Daniela Caccamo, Nadia Ferlazzo, Monica Currò, Sergio Ricca, Riccardo Ientile
Recent evidence indicated that transglutaminase 2 (TG2) is involved in the adaptive immune response. Peripheral blood mononuclear cells (PBMC) have largely been used to characterize molecular mechanisms occurring in the activation of immune response. Given that the maintenance of immune system functions requires an optimal vitamin D status, we aimed to assess the involvement of TG2/NF-κB signaling in cytokine production in PBMC isolated from adult subjects with different vitamin D status. We observed TG2 up-regulation and a significant positive correlation between TG2 expression and tumor necrosis factor (TNF)-α mRNA levels in PBMC of recruited patients...
November 16, 2018: Medical Sciences: Open Access Journal
Jinchao Li, Armina-Lyn M Frederick, Yu Jin, Chi Guo, Hang Xiao, Richard J Wood, Zhenhua Liu
SCOPE: Our previous study showed that obesity-promoted inflammation is responsible for the activation of the intestinal tumorigenic Wnt-signaling. The present study aimed to test a dietary strategy, dietary supplementation with a high dose of vitamin D (VD) or its combination with sulforaphane (SFN), to inhibit intestinal inflammation and obesity-associated tumorigenesis. METHODS AND RESULTS: Apc1638N mice were randomly divided into 4 groups: LF, a low fat diet (10 kcal% fat) with 200 IU VD; HF, a high fat diet (60 kcal% fat) with 200 IU VD; HFD: a high fat diet with 5,000 IU VD; and HFDS, a high fat diet plus 5,000 IU VD and 0...
November 17, 2018: Molecular Nutrition & Food Research
Amie L T Romney, Erin M Davis, Meranda M Corona, Josiah T Wagner, Jason E Podrabsky
The mechanisms that integrate environmental signals into developmental programs remain largely uncharacterized. Nuclear receptors (NRs) are ligand-regulated transcription factors that orchestrate the expression of complex phenotypes. The vitamin D receptor (VDR) is an NR activated by 1α,25-dihydroxyvitamin D3 [1,25(OH)2 D3 ], a hormone derived from 7-dehydrocholesterol (7-DHC). VDR signaling is best known for regulating calcium homeostasis in mammals, but recent evidence suggests a diversity of uncharacterized roles...
November 16, 2018: Proceedings of the National Academy of Sciences of the United States of America
H Miao, J Xu, D Xu, X Ma, X Zhao, L Liu
Paclitaxel is used for the treatment of several types of cancers. However, one of the significant limiting complications of paclitaxel is painful peripheral neuropathy during its therapy. In this study we examined the engagement of antioxidative signal pathway of the dorsal root ganglion (DRG) in mechanical and thermal hypersensitivity evoked by paclitaxel. Behavioral test was performed to determine mechanical and thermal sensitivity in rats. Western Blot analysis and ELISA were used to examine expression of Nrf2-antioxidant response element (ARE) and superoxide dismutases (SOD); and the levels of products of oxidative stress in the DRG...
October 23, 2018: Physiological Research
Lili Xin, Bizhong Che, Bingzhong Zhai, Qiulin Luo, Chen Zhang, Jianshu Wang, Shengli Wang, Guoqiang Fan, Zhiyong Liu, Jialiang Feng, Zengli Zhang
Vitamin D3 is reported to be involved in the regulation of inflammatory processes. In this study, biomarkers related to oxidative stress and inflammation were investigated to clarify the protective effects and possible mechanism of 1,25-dihydroxy vitamin D3 (1,25-(OH)2 D3 ) on PM2.5 -induced inflammatory response. In the in vitro study using human bronchial epithelial (HBE) cells, aqueous extracts of PM2.5 could induce oxidative damage which is characterized by significant increases in production of reactive oxygen species, malonaldehyde concentration, and protein expression of HSPA1A and HO-1...
November 14, 2018: Inflammation
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