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CYP24A1

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https://www.readbyqxmd.com/read/28636886/sirt1-enzymatically-potentiates-1-25-dihydroxyvitamin-d3-signaling-via-vitamin-d-receptor-deacetylation
#1
Marya S Sabir, Chengcheng Hu, Zainab Khan, 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...
June 18, 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
#2
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 6, 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
#3
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
#4
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
#5
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
#6
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
#7
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...
May 18, 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
#8
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
#9
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
https://www.readbyqxmd.com/read/28586461/genetically-low-vitamin-d-concentrations-and-myopic-refractive-error-a-mendelian-randomization-study
#10
Gabriel Cuellar-Partida, Katie M Williams, Seyhan Yazar, Jeremy A Guggenheim, Alex W Hewitt, Cathy Williams, Jie Jin Wang, Pik-Fang Kho, Seang Mei Saw, Ching-Yu Cheng, Tien Yin Wong, Tin Aung, Terri L Young, J Willem L Tideman, Jost B Jonas, Paul Mitchell, Robert Wojciechowski, Dwight Stambolian, Pirro Hysi, Christopher J Hammond, David A Mackey, Robyn M Lucas, Stuart MacGregor
Background: Myopia prevalence has increased in the past 20 years, with many studies linking the increase to reduced time spent outdoors. A number of recent observational studies have shown an inverse association between vitamin D [25(OH)D] serum levels and myopia. However, in such studies it is difficult to separate the effects of time outdoors and vitamin D levels. In this work we use Mendelian randomization (MR) to assess if genetically determined 25(OH)D levels contribute to the degree of myopia...
June 6, 2017: International Journal of Epidemiology
https://www.readbyqxmd.com/read/28579119/function-of-the-vitamin-d-endocrine-system-in-mammary-gland-and-breast-cancer
#11
REVIEW
JoEllen Welsh
The nuclear receptor for 1α,25-dihydroxycholecalciferol (1,25D), the active form of vitamin D, has anti-tumor actions in many tissues. The vitamin D receptor (VDR) is expressed in normal mammary gland and in many human breast cancers suggesting it may represent an important tumor suppressor gene in this tissue. When activated by 1,25D, VDR modulates multiple cellular pathways including those related to energy metabolism, terminal differentiation and inflammation. There is compelling pre-clinical evidence that alterations in vitamin D status affect breast cancer development and progression, while clinical and epidemiological data are suggestive but not entirely consistent...
June 1, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28578001/1%C3%AE-25-dihydroxyvitamin-d3-enhances-trpv6-transcription-through-p38-mapk-activation-and-gadd45-expression
#12
Michiyasu Ishizawa, Daisuke Akagi, Jumpei Yamamoto, Makoto Makishima
The active form of vitamin D, 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], acts as a ligand for the vitamin D receptor (VDR), and regulates various physiological processes, including calcium and bone metabolism, cellular growth and differentiation, immunity and cardiovascular function. A number of vitamin D derivatives have been synthesized for the treatment of cancer and inflammatory disease, but the adverse effect of hypercalcemic activity due to intestinal calcium absorption has limited wide clinical application...
May 31, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28575224/response-to-antenatal-cholecalciferol-supplementation-is-associated-with-common-vitamin-d-related-genetic-variants
#13
Rebecca J Moon, Nicholas C Harvey, Cyrus Cooper, Stefania D'Angelo, Elizabeth M Curtis, Sarah R Crozier, Sheila J Barton, Sian M Robinson, Keith M Godfrey, Nikki J Graham, John W Holloway, Nicholas J Bishop, Stephen Kennedy, Aris T Papageorghiou, Inez Schoenmakers, Robert Fraser, Saurabh V Gandhi, Ann Prentice, Hazel M Inskip, M Kassim Javaid
Context: Single nucleotide polymorphisms (SNP) in genes related to vitamin D metabolism have been associated with serum 25-hydroxyvitamin D [25(OH)D] concentration, but these relationships have not been examined following antenatal cholecalciferol supplementation. Objective: To determine whether SNPs in DHCR7, CYP2R1, CYP24A1 and GC are associated with the response to gestational cholecalciferol supplementation. Design: Within-randomization-group analysis of the MAVIDOS trial of antenatal cholecalciferol supplementation...
May 29, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28548312/vitamin-d-dependent-rickets-type-1b-25-hydroxylase-deficiency-a-rare-condition-or-a-misdiagnosed-condition
#14
Molin A, Wiedemann A, Demers N, Kaufmann M, Do Cao J, Mainard L, Dousset B, Journeau P, Abeguile G, Coudray N, Mittre H, Richard N, Weryha G, Sorlin A, Jones G, Kottler Ml, Feillet F
Vitamin D requires a two-step activation by hydroxylation: the first step is catalyzed by hepatic 25-hydroxylase (CYP2R1, 11p15.2), and the second one is catalyzed by renal 1α-hydroxylase (CYP27B1, 12q13.1), which produces the active hormonal form of 1,25-(OH)2 D. Mutations of CYP2R1 have been associated with Vitamin D-dependent rickets type 1B (VDDR1B), a very rare condition that has only been reported to affect 4 families to date. We describe 7 patients from two unrelated families who presented with homozygous loss-of-function mutations of CYP2R1...
May 26, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28526240/endocrine-actions-of-vitamin-d-in-skin-relevance-for-photocarcinogenesis-of-non-melanoma-skin-cancer-and-beyond
#15
REVIEW
Jörg Reichrath, Roman Saternus, Thomas Vogt
The skin represents a pivotal organ for the human body's vitamin D endocrine system, being both the site of ultraviolet (UV)-B-induced vitamin D synthesis and a target tissue for the pluripotent effects of 1,25(OH)2D3 and other biologically active vitamin D metabolites. As many other steroid hormones, 1,25(OH)2D3 exerts its effects via two independent signal transduction pathways: the classical genomic and the non-genomic pathway. While non-genomic effects of 1,25(OH)2D3 are in part exerted via effects on intracellular calcium, genomic effects are mediated by the vitamin D receptor (VDR)...
May 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28506446/serum-24-25-dihydroxyvitamin-d3-response-to-native-vitamin-d2%C3%A2-and%C3%A2-d3-supplementation-in-patients-with-chronic-kidney-disease%C3%A2-on%C3%A2-hemodialysis
#16
Laura A Graeff-Armas, Martin Kaufmann, Elizabeth Lyden, Glenville Jones
BACKGROUND & AIMS: While vitamin D deficiency is common in patients with end stage renal disease on dialysis and treatment with Vitamin D2 and Vitamin D3 is becoming increasingly common in these patients, little is known about 24,25(OH)2D3 metabolite production. Some authors report that the CYP24A1 enzyme is upregulated in CKD, but reports of low serum levels of 24,25(OH)2D3 in these patients bring this into question. Lack of substrate or increased clearance of the metabolite have been proposed as possible causes...
April 30, 2017: Clinical Nutrition: Official Journal of the European Society of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28492801/orthotopic-tumorgrafts-in-nude-mice-as-a-model-to-evaluate-calcitriol-effects-in-breast-cancer
#17
V C N Fonseca-Filho, M L H Katayama, E C Lyra, D A Maria, R A Basso, S Nonogaki, J M Guerra, S Maistro, J C G S Góes, M A A K Folgueira
Objectives: To establish a tumorgraft model, from freshly collected breast cancer samples, which were directly implanted in nude mice, to study calcitriol effects. Methods: Breast cancer samples collected from 12 patients were orthotopically implanted into nude mice. Animals were treated with weekly intratumoral injections of calcitriol 3 μg/Kg, which was previously shown to induce peak serum calcitriol levels in the predicted therapeutic range. Results: Success engraftment rate was 25%...
May 4, 2017: Brazilian Journal of Biology, Revista Brasleira de Biologia
https://www.readbyqxmd.com/read/28470390/biallelic-mutations-in-cyp24a1-or-slc34a1-as-a-cause-of-infantile-idiopathic-hypercalcemia-iih-with-vitamin-d-hypersensitivity-molecular-study-of-11-historical-iih-cases
#18
Ewa Pronicka, Elżbieta Ciara, Paulina Halat, Agnieszka Janiec, Marek Wójcik, Elżbieta Rowińska, Dariusz Rokicki, Paweł Płudowski, Ewa Wojciechowska, Aldona Wierzbicka, Janusz B Książyk, Agnieszka Jacoszek, Martin Konrad, Karl P Schlingmann, Mieczysław Litwin
Idiopathic infantile hypercalcemia (IIH) is a mineral metabolism disorder characterized by severe hypercalcemia, failure to thrive, vomiting, dehydration, and nephrocalcinosis. The periodical increase in incidence of IIH, which occurred in the twentieth century in the United Kingdom, Poland, and West Germany, turned out to be a side effect of rickets over-prophylaxis. It was recently discovered that the condition is linked to two genes, CYP24A1 and SLC34A1. The aim of the study was to search for pathogenic variants of the genes in adult persons who were shortlisted in infancy as IIH caused by "hypersensitivity to vit...
May 3, 2017: Journal of Applied Genetics
https://www.readbyqxmd.com/read/28456639/-hypercalcemia-and-inactive-mutation-of-cyp24a1-case-study-and-literature-review
#19
Alexandre Seidowsky, Cédric Villain, Eve Vilaine, Roselyne Baudoin, Antoine Tabarin, Marie-Laure Kottler, Étienne Cavalier, Jean-Claude Souberbielle, Ziad A Massy
We present the case of a family whose members have high levels of serum calcium (hypercalcaemia) by loss of function of the enzyme vitamin D 24-hydroxylase due to bi-allelic mutations in the CYP24A1 gene: c.443 T>C (p.Leu148Pro) and c.1187 G>A (p.Arg396Gln). 24-VITD hydroxylase is a key player in regulating the circulating calcitriol, its tissue concentration and its biological effects. Transmission is recessive. The estimated prevalence of stones in the affected subjects is estimated between 10 and 15%...
May 2017: Néphrologie & Thérapeutique
https://www.readbyqxmd.com/read/28453395/association-of-vitamin-d-pathway-snps-and-clinical-response-to-interferon-in-a-cohort-of-hbeag-negative-patients
#20
Jessica Cusato, Lucio Boglione, Amedeo De Nicolò, Rosaria Imbornone, Chiara Simona Cardellino, Valeria Ghisetti, Chiara Carcieri, Giuseppe Cariti, Giovanni Di Perri, Antonio D'Avolio
AIM: Vitamin D modulates biological processes; an influence of vitamin D levels and genetic variants was identified concerning hepatitis B virus infection. We evaluated the role of some SNPs of vitamin D pathway genes in some clinical features of hepatitis B affected patients treated with pegylated interferon. METHODS: We investigated SNPs in IL-28B, CYP27B1, CYP27A1, CYP24A1, VDBP and VDR genes, through real-time PCR. RESULTS:  VDRApaI SNP was associated to viral load and HBsAg presence at different timings...
April 28, 2017: Pharmacogenomics
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