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CYP24A1

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https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#1
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28811712/association-between-cyp24a1-polymorphisms-and-the-risk-of-colonic-polyps-and-colon-cancer-in-a-chinese-population
#2
Xue-Qi Chen, Jia-Yu Mao, Wen-Bin Li, Jian Li, Hong Yang, Jia-Ming Qian, Jing-Nan Li
AIM: To determine the pathogenesis and potential single nucleotide polymorphisms (SNPs) as screening sites for colonic polyps, colon cancer and ulcerative colitis, and to analyze the possible association between these genetic polymorphisms and the three diseases. METHODS: We evaluated genetic polymorphisms in 144 newly diagnosed colonic polyp patients, 96 colon cancer patients and 44 ulcerative colitis patients. The four SNPs genotyped were rs4809957, rs6068816, rs6091822 and rs8124792...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28808890/vitamin-d-activity-and-metabolism-in-bone
#3
REVIEW
Paul H Anderson
PURPOSE OF REVIEW: In addition to the actions of the endocrine hormone, 1alpha,25-dihydroxyvitamin D (1,25(OH)2D) in stimulating intestinal calcium absorption, the regulation of bone mineral metabolism by 1,25(OH)2D is also considered an important contributor to calcium homeostasis. However, recent evidence suggest that 1,25(OH)2D acting either via endocrine or autocrine pathways plays varied roles in bone, which suggests that vitamin D contributes to the maintenance of bone mineral in addition to its catabolic roles...
August 14, 2017: Current Osteoporosis Reports
https://www.readbyqxmd.com/read/28808057/a-kidney-specific-genetic-control-module-in-mice-governs-endocrine-regulation-of-the-cytochrome-p450-gene-cyp27b1-essential-for-vitamin-d3-activation
#4
Mark B Meyer, Nancy A Benkusky, Martin Kaufmann, Seong Min Lee, Melda Onal, Glenville Jones, J Wesley Pike
The vitamin D endocrine system regulates mineral homeostasis through its activities in the intestine, kidney, and bone. Terminal activation of vitamin D3 to its hormonal form, 1,25(OH)2D3, occurs in the kidney via the cytochrome P450 enzyme CYP27B1. Despite its importance in vitamin D metabolism, the molecular mechanisms underlying the regulation of the gene for this enzyme, Cyp27b1, are unknown. Here, we identified a kidney-specific control module governed by a renal cell-specific chromatin structure located distal to Cyp27b1 that mediates unique basal and parathyroid hormone (PTH)-, fibroblast growth factor 23 (FGF23)-, and 1,25(OH)2D3-mediated regulation of Cyp27b1 expression...
August 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28768705/effects-of-vitamin-d2-supplementation-on-vitamin-d3-metabolism-in-health-and-ckd
#5
Zona Batacchi, Cassianne Robinson-Cohen, Andrew N Hoofnagle, Tamara Isakova, Bryan Kestenbaum, Kevin J Martin, Myles S Wolf, Ian H de Boer
BACKGROUND AND OBJECTIVES: Vitamin D supplements are prescribed to correct low circulating concentrations of 25-hydroxyvitamin D. In CKD, vitamin D metabolism is complicated by decreased conversion of 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D by CYP27B1 and possibly decreased conversion of 25-hydroxyvitamin D to 24,25-dihydroxyvitamin D by CYP24A1. The aim of this study was to determine the effects of vitamin D2 supplementation on vitamin D metabolism in health and CKD. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We conducted a treatment-only intervention study of 25 individuals with CKD (eGFR<60 ml/min per 1...
August 2, 2017: Clinical Journal of the American Society of Nephrology: CJASN
https://www.readbyqxmd.com/read/28754147/design-and-implementation-of-a-custom-next-generation-sequencing-panel-for-selected-vitamin-d-associated-genes
#6
Katherine Angela Benson, Sourabh Chand, Alexander Peter Maxwell, Laura Jane Smyth, Jill Kilner, Richard Borrows, Amy Jayne McKnight
BACKGROUND: Biologically active vitamin D has an important regulatory role within the genome. It binds the vitamin D receptor (VDR) in order to control the expression of a wide range of genes as well as interacting with the epigenome to modify chromatin and methylation status. Vitamin D deficiency is associated with several human diseases including end-stage renal disease. METHODS: This article describes the design and testing of a custom, targeted next generation sequencing (NGS) panel for selected vitamin D associated genes...
July 28, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28716761/recent-developments-for-introducing-a-hexafluoroisopropanol-unit-into-the-vitamin-d-side-chain
#7
REVIEW
Fumihiro Kawagoe, Toru Sugiyama, Motonari Uesugi, Atsushi Kittaka
Among numerous studies on synthetic approaches to and the biological activities of vitamin D analogues, we herein focused on falecalcitriol, an analogue of calcitriol (1α,25-dihydroxyvitamin D3), in which a 26,26,26,27,27,27-hexafluoroisopropanol unit has been introduced into the side chain. Falecalcitriol was designed to escape from the metabolism of CYP24A1 and has been used as a drug to treat secondary hypoparathyroidism since 2001. Its metabolite, the 23-hydroxy form, retains biological activity and resistants to further metabolism...
July 14, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28676457/on-the-role-of-classical-and-novel-forms-of-vitamin-d-in-melanoma-progression-and-management
#8
REVIEW
Andrzej T Slominski, Anna A Brozyna, Cezary Skobowiat, Michal A Zmijewski, Tae-Kang Kim, Zorica Janjetovic, Allen S Oak, Wojciech Jozwicki, Anton M Jetten, Rebecca S Mason, Craig Elmets, We Li, Robert M Hoffman, Robert C Tuckey
Melanoma represents a significant clinical problem affecting a large segment of the population with a relatively high incidence and mortality rate. Ultraviolet radiation (UVR) is an important etiological factor in malignant transformation of melanocytes and melanoma development. UVB, while being a full carcinogen in melanomagenesis, is also necessary for the cutaneous production of vitamin D3 (D3). Calcitriol (1,25(OH)2D3) and novel CYP11A1-derived hydroxyderivatives of D3 show anti-melanoma activities and protective properties against damage induced by UVB...
July 1, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28673024/ancestry-adjusted-vitamin-d-metabolite-concentrations-in-association-with-cytochrome-3a-cyp3a-polymorphisms
#9
Robin Taylor Wilson, Loren D Masters, Jill S Barnholtz-Sloan, Anna C Salzberg, Terryl J Hartman
This study investigates the association between genetic polymorphisms in CYP2R1, CYP24A1 and the CYP3A family with non-summer plasma concentrations of 25(OH)D3 and proportion 24,25(OH)2D3 among healthy individuals of Sub-Saharan African and European ancestry matched on age (±5 years; n = 188 in each ancestral group) in central suburban Pennsylvania (2006-09). Vitamin D metabolites were measured using high-performance liquid chromatography/tandem mass spectrometry. Paired multiple regression and adjusted least square means analyses were used to test for associations between genotype and log-transformed metabolite concentrations, adjusted for age, sex, West African genetic ancestry proportion, body mass index, oral contraceptive (OC) use, tanning bed use, vitamin D intake, days from summer solstice, time of day, and isoforms of the vitamin D receptor (VDR) and vitamin D binding protein...
June 30, 2017: American Journal of Epidemiology
https://www.readbyqxmd.com/read/28665937/cholecalciferol-decreases-inflammation-and-improves-vitamin-d-regulatory-enzymes-in-lymphocytes-in-the-uremic-environment-a-randomized-controlled-pilot-trial
#10
José Tarcisio G Carvalho, Marion Schneider, Lilian Cuppari, Caren C Grabulosa, Danilo T Aoike, Beata Marie Q Redublo, Marcelo C Batista, Miguel Cendoroglo, Rosa Maria Moyses, Maria Aparecida Dalboni
It has been reported that vitamin D regulates the immune system. However, whether vitamin D repletion modulates inflammatory responses in lymphocytes from dialysis patients is unclear. In the clinical trial, thirty-two (32) dialysis patients with 25 vitamin D ≤ 20ng/mL were randomized to receive either supplementation of cholecalciferol 100,000 UI/week/3 months (16 patients) or placebo (16 patients). In the in vitro study, B and T lymphocytes from 12 healthy volunteers (HV) were incubated with or without uremic serum in the presence or absence of 25 or 1,25 vitamin D...
2017: PloS One
https://www.readbyqxmd.com/read/28665452/genetic-polymorphisms-of-vitamin-d-metabolism-genes-and-serum-level-of-vitamin-d-in-colorectal-cancer
#11
Verônica Marques Vidigal, Pedro Nazareth Aguiar Junior, Tiago Donizetti Silva, Juliana de Oliveira, Célia Aparecida Marques Pimenta, Aledson Vitor Felipe, Nora Manoukian Forones
BACKGROUND: The metabolism of vitamin D is complex, its receptor (VDR) and proteins encoded by the genes CYP27B2 and CYP24A1 can influence vitamin D serum levels. The aim of this study was to investigate the relationship of the polymorphisms of VDR (ApaI and BsmI), CYP27B1 and CYP24A1 with serum vitamin D levels in both forms, 25(OH)D3 (circulating form) and 1,25(OH)2D3 (active form), in colorectal cancer (CRC) patients. METHODS: One hundred fifty-two CRC patients and 321 controls were included...
June 19, 2017: International Journal of Biological Markers
https://www.readbyqxmd.com/read/28636886/sirt1-enzymatically-potentiates-1-25-dihydroxyvitamin-d3-signaling-via-vitamin-d-receptor-deacetylation
#12
Marya S Sabir, Zainab Khan, Chengcheng Hu, Michael A Galligan, Christopher M Dussik, Sanchita Mallick, Angelika Dampf Stone, Shane F Batie, Elizabeth T Jacobs, G Kerr Whitfield, Mark R Haussler, Michael C Heck, Peter W Jurutka
The hormonal metabolite of vitamin D, 1,25-dihydroxyvitamin D3 (1,25D), binds to the vitamin D receptor (VDR) and promotes heterodimerization of VDR with a retinoid-X-receptor (RXR) to genomically regulate diverse cellular processes. Herein, it is revealed for the first time that VDR is post-translationally acetylated, and that VDR immunoprecipitated from human embryonic kidney (HEK293) cells displays a dramatic decrease in acetylated receptor in the presence of 1,25D-ligand, sirtuin-1 (SIRT1) deacetylase, or the resveratrol activator of SIRT1...
September 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28622535/vitamin-d-mediates-the-relationship-between-placental-cathelicidin-and-group-b-streptococcus-colonization-during-pregnancy
#13
Christine C Akoh, Eva K Pressman, Corrie M Whisner, Carrie Thomas, Chang Cao, Tera Kent, Elizabeth Cooper, Kimberly O O'Brien
Vitamin D is thought to modulate innate immune responses, and recent studies have highlighted the autocrine and paracrine functions of vitamin D in the placenta. Our objective was to determine the relationship between maternal vitamin D status and placental antimicrobial peptide (AMP) expression in a group of racially and ethnically diverse pregnant adolescents. In this study, 158 pregnant adolescents were recruited from the Rochester Adolescent Maternity Program (RAMP) in Rochester, NY. Maternal serum concentrations of the vitamin D biomarkers, 25-hydroxyvitamin D (25(OH)D) and 1,25-dihydroxyvitamin D (1,25(OH)2D), were measured at mid-gestation (∼26 weeks) and at delivery...
June 2017: Journal of Reproductive Immunology
https://www.readbyqxmd.com/read/28619151/effects-of-vitamin-d-and-its-metabolites-on-cell-viability-and-staphylococcus-aureus-invasion-into-bovine-mammary-epithelial-cells
#14
Yuan Yue, Lone Hymøller, Søren K Jensen, Charlotte Lauridsen, Stig Purup
Vitamin D has been found have various biological effects that may be potent in preventing bovine mastitis. Two forms of vitamin D, vitamin D2 (D2) and vitamin D3 (D3), can be hydroxylated to functional metabolites in cattle. The objectives of the present study were to investigate the potential of vitamin D compounds for controlling bovine mastitis using in vitro cell models, and to compare the differences between D2 and D3 compounds. Results showed that D2 compounds have comparable effects to their D3 analogues on inhibiting MAC-T cell viability in vitro...
May 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/28601511/synthesis-molecular-modelling-and-cyp24a1-inhibitory-activity-of-novel-of-e-n-2-1h-imidazol-1-yl-2-phenylethyl-3-4-styrylbenzamides
#15
Ismail M Taban, Jinge Zhu, Hector F DeLuca, Claire Simons
CYP24A1 (25-hydroxyvitamin D-24-hydroxylase) is a useful enzyme target for a range of medical conditions including cancer, cardiovascular and autoimmune disease, which show elevated CYP24A1 levels and corresponding reduction of calcitriol (the biologically active form of vitamin D). A series of (E)-N-(2-(1H-imidazol-1-yl)-2-(phenylethyl)-3/4-styrylbenzamides have been synthesised using an efficient synthetic route and shown to be potent inhibitors of CYP24A1 (IC50 0.11-0.35μM) compared with the standard ketoconazole...
May 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28594304/role-of-vitamin-d-pathway-gene-polymorphisms-on-rifampicin-plasma-and-intracellular-pharmacokinetics
#16
Sarah Allegra, Giovanna Fatiguso, Andrea Calcagno, Lorena Baietto, Ilaria Motta, Fabio Favata, Jessica Cusato, Stefano Bonora, Giovanni Di Perri, Antonio D'Avolio
AIM: We retrospectively evaluate the pharmacogenetic role of single nucleotide polymorphisms involved in rifampicin transport (SLCO1B1, MDR1 and PXR genes) and vitamin D (VDR, CYP24A1 and CYP27B1 genes) metabolism and activity on drug plasma and intracellular concentrations. PATIENTS & METHODS: Rifampicin Cmax and Ctrough were measured at weeks 2 and 4 using Ultra-Performance Liquid Chromatography-tandem mass spectroscopy methods. Allelic discrimination was performed by real-time polymerase chain reaction...
June 8, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28594127/no-clear-support-for-a-role-for-vitamin-d-in-parkinson-s-disease-a-mendelian-randomization-study
#17
Susanna C Larsson, Andrew B Singleton, Mike A Nalls, J Brent Richards
BACKGROUND: Observational studies have found that relative to healthy controls, patients with Parkinson's disease have lower circulating concentrations of 25-hydroxyvitamin D, a clinical biomarker of vitamin D status. However, the causality of this association is uncertain. We undertook a Mendelian randomization study to investigate whether genetically decreased 25-hydroxyvitamin D concentrations are associated with PD to minimize confounding and prevent bias because of reverse causation...
June 8, 2017: Movement Disorders: Official Journal of the Movement Disorder Society
https://www.readbyqxmd.com/read/28591703/vitamin-d-receptor-activation-reduces-vcap-xenograft-tumor-growth-and-counteracts-erg-activity-despite-induction-of-tmprss2-erg
#18
Justin M Roberts, Rebeca San Martin, D Badrajee Piyarathna, James G MacKrell, Guilherme V Rocha, Jeffery A Dodge, Cristian Coarfa, Venkatesh Krishnan, David R Rowley, Nancy L Weigel
Whether vitamin D is chemopreventive and/or has potential therapeutically in prostate cancer is unresolved. One confounding factor is that many prostate cancers express a TMPRSS2:ERG fusion gene whose expression is increased both by androgens and by vitamin D receptor (VDR) activation. Two challenges that limit VDR agonist use clinically are hypercalcemia and the cooperation of VDR with ERG to hyper-induce the 1α,25-dihydroxyvitamin D3 metabolizing enzyme, CYP24A1, thus reducing VDR activity. Using the VCaP TMPRSS2:ERG positive cell line as a model, we found that a nonsecosteroidal CYP24A1 resistant VDR agonist, VDRM2, substantially reduces growth of xenograft tumors without inducing hypercalcemia...
July 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589636/25-hydroxyvitamin-d3-and-its-c-3-epimer-are-elevated-in-the-skin-and-serum-of-skh-1-mice-supplemented-with-dietary-vitamin-d3
#19
Matthew D Teegarden, Amanda R Campbell, Jessica L Cooperstone, Kathleen L Tober, Steven J Schwartz, Tatiana M Oberyszyn
SCOPE: UV exposure is a risk factor for keratinocyte carcinoma (KC) while critical for endogenous vitamin D production. We investigated dietary modulation of skin and serum 25-hydroxyvitamin D3 (25OHD3 ) and its C-3 epimer (C3epi) in a mouse model of KC. C3epi is an under-investigated metabolite of vitamin D with respect to its biological implications. METHODS AND RESULTS: Male and female Skh-1 mice were supplemented with 25, 150 or 1000 IU/kg diet vitamin D3 for 25 weeks, with some exposed to UV light...
June 7, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28589382/vitamin-d-receptor-and-progesterone-receptor-protein-and-gene-expression-in-papillary-thyroid-carcinomas-associations-with-histological-features
#20
M P Yavropoulou, G Panagiotou, K Topouridou, G Karayannopoulou, T Koletsa, T Zarampoukas, A Goropoulos, E Chatzaki, J G Yovos, K Pazaitou-Panayiotou
PURPOSE: Vitamin D receptor (VDR) and progesterone receptor (PR) expression has been described in papillary thyroid carcinoma (PTC) but data regarding association with tumor histological characteristics and localization of the protein expression are scarce. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens from 45 patients with PTC (cases) were retrieved and tumor histological data were recorded. We analyzed gene and protein expression of VDR and PR and gene expression of vitamin D-inactivating 24-hyroxylase (CYP24A1) and the activating 1-alpha-hydroxylase (CYP27B1) enzymes in follicular cancer cells and the adjacent non-neoplastic thyroid tissue (NNTT)...
June 6, 2017: Journal of Endocrinological Investigation
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