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  1 / 417 MEDLINE  
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[PMID]:29227993
[Au] Autor:McGurk PD; Swartz ME; Chen JW; Galloway JL; Eberhart JK
[Ad] Endereço:Department of Molecular Biosciences, University of Texas at Austin, Austin, TX, United States of America.
[Ti] Título:In vivo zebrafish morphogenesis shows Cyp26b1 promotes tendon condensation and musculoskeletal patterning in the embryonic jaw.
[So] Source:PLoS Genet;13(12):e1007112, 2017 12.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Integrated development of diverse tissues gives rise to a functional, mobile vertebrate musculoskeletal system. However, the genetics and cellular interactions that drive the integration of muscle, tendon, and skeleton are poorly understood. In the vertebrate head, neural crest cells, from which cranial tendons derive, pattern developing muscles just as tendons have been shown to in limb and trunk tissue, yet the mechanisms of this patterning are unknown. From a forward genetic screen, we determined that cyp26b1 is critical for musculoskeletal integration in the ventral pharyngeal arches, particularly in the mandibulohyoid junction where first and second arch muscles interconnect. Using time-lapse confocal analyses, we detail musculoskeletal integration in wild-type and cyp26b1 mutant zebrafish. In wild-type fish, tenoblasts are present in apposition to elongating muscles and condense in discrete muscle attachment sites. In the absence of cyp26b1, tenoblasts are generated in normal numbers but fail to condense into nascent tendons within the ventral arches and, subsequently, muscles project into ectopic locales. These ectopic muscle fibers eventually associate with ectopic tendon marker expression. Genetic mosaic analysis demonstrates that neural crest cells require Cyp26b1 function for proper musculoskeletal development. Using an inhibitor, we find that Cyp26 function is required in a short time window that overlaps the dynamic window of tenoblast condensation. However, cyp26b1 expression is largely restricted to regions between tenoblast condensations during this time. Our results suggest that degradation of RA by this previously undescribed population of neural crest cells is critical to promote condensation of adjacent scxa-expressing tenoblasts and that these condensations are subsequently required for proper musculoskeletal integration.
[Mh] Termos MeSH primário: Desenvolvimento Embrionário/genética
Desenvolvimento Maxilofacial/genética
Morfogênese/genética
Ácido Retinoico 4 Hidroxilase/genética
[Mh] Termos MeSH secundário: Animais
Padronização Corporal/genética
Regulação da Expressão Gênica no Desenvolvimento
Arcada Osseodentária/embriologia
Desenvolvimento Muscular/genética
Músculo Esquelético/embriologia
Músculo Esquelético/metabolismo
Tendões/embriologia
Tendões/crescimento & desenvolvimento
Peixe-Zebra/embriologia
Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL
[Nm] Nome de substância:
EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase)
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171212
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1007112


  2 / 417 MEDLINE  
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[PMID]:29337257
[Au] Autor:Dimopoulou M; Verhoef A; Gomes CA; van Dongen CW; Rietjens IMCM; Piersma AH; van Ravenzwaay B
[Ad] Endereço:Division of Toxicology, Wageningen University, The Netherlands; National Institute of Public Health and the Environment (RIVM), Bilthoven, The Netherlands. Electronic address: myrto.dimopoulou@wur.nl.
[Ti] Título:A comparison of the embryonic stem cell test and whole embryo culture assay combined with the BeWo placental passage model for predicting the embryotoxicity of azoles.
[So] Source:Toxicol Lett;286:10-21, 2018 Apr.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:In the present study, we show the value of combining toxico-dynamic and -kinetic in vitro approaches for embryotoxicity testing of azoles. Both the whole embryo culture (WEC) and the embryonic stem cells test (EST) predicted the in vivo potency ranking of twelve tested azoles with moderate accuracy. Combining these results with relative placental transfer rates (Papp values) as determined in the BeWo cell culture model, increased the predictability of both WEC and EST, with R values increasing from 0.51 to 0.87 and from 0.35 to 0.60, respectively. The comparison of these in vitro systems correlated well (R = 0.67), correctly identifying the in vivo strong and weak embryotoxicants. Evaluating also specific gene responses related with the retinoic acid and sterol biosynthesis pathways, which represent the toxicological and fungicidal mode of action of azoles respectively in the WEC and EST, we observed that the differential regulation of Dhrs3 and Msmo1 reached higher magnitudes in both systems compared to Cyp26a1 and Cyp51. Establishing sensitive biomarkers across the in vitro systems for studying the underlying mechanism of action of chemicals, such as azoles, is valuable for comparing alternative in vitro models and for improving insight in the mechanism of developmental toxicity of chemicals.
[Mh] Termos MeSH primário: Azóis/toxicidade
Bioensaio
Embrião de Mamíferos/efeitos dos fármacos
Células-Tronco Embrionárias Murinas/efeitos dos fármacos
Placenta/efeitos dos fármacos
Teratogênios/toxicidade
Testes de Toxicidade/métodos
[Mh] Termos MeSH secundário: Oxirredutases do Álcool/genética
Oxirredutases do Álcool/metabolismo
Animais
Transporte Biológico
Diferenciação Celular/efeitos dos fármacos
Linhagem Celular
Relação Dose-Resposta a Droga
Técnicas de Cultura Embrionária
Embrião de Mamíferos/metabolismo
Embrião de Mamíferos/patologia
Feminino
Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos
Seres Humanos
Cinética
Camundongos
Oxigenases de Função Mista/genética
Oxigenases de Função Mista/metabolismo
Células-Tronco Embrionárias Murinas/metabolismo
Células-Tronco Embrionárias Murinas/patologia
Miócitos Cardíacos/efeitos dos fármacos
Miócitos Cardíacos/metabolismo
Miócitos Cardíacos/patologia
Placenta/metabolismo
Placenta/patologia
Gravidez
Reprodutibilidade dos Testes
Ácido Retinoico 4 Hidroxilase/genética
Ácido Retinoico 4 Hidroxilase/metabolismo
Medição de Risco
Esterol 14-Desmetilase/genética
Esterol 14-Desmetilase/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Azoles); 0 (Teratogens); EC 1.- (Mixed Function Oxygenases); EC 1.1.- (Alcohol Oxidoreductases); EC 1.1.1.71 (DHRS3 protein, mouse); EC 1.14.13.70 (Cyp51 protein, mouse); EC 1.14.13.70 (Sterol 14-Demethylase); EC 1.14.13.72 (methylsterol monooxygenase); EC 1.14.14.1 (Cyp26a1 protein, mouse); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180220
[Lr] Data última revisão:
180220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180117
[St] Status:MEDLINE


  3 / 417 MEDLINE  
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[PMID]:28436029
[Au] Autor:Zhang HL; Yang ZQ; Duan CC; Geng S; Wang K; Yu HF; Yue ZP; Guo B
[Ad] Endereço:College of Veterinary Medicine, Jilin University, Changchun, P. R. China.
[Ti] Título:WNT4 acts downstream of BMP2 to mediate the regulation of ATRA signaling on RUNX1 expression: Implications for terminal differentiation of antler chondrocytes.
[So] Source:J Cell Physiol;233(2):1129-1145, 2018 Feb.
[Is] ISSN:1097-4652
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Although ATRA is involved in regulating the proliferation and differentiation of chondrocytes, its underlying mechanism remains unknown. Here we showed that ATRA could stimulate the proliferation of antler chondrocytes and expression of COL X and MMP13 which were two well-known markers for hypertrophic chondrocytes. Silencing of CRABP2 prevented the induction of ATRA on chondrocyte terminal differentiation, while overexpression of CRABP2 exhibited the opposite effects. CYP26A1 and CYP26B1 weakened the sensitivity of antler chondrocytes to ATRA. Further analysis evidenced that ATRA might induce chondrocyte terminal differentiation and modulate the expression of BMP2, WNT4, and RUNX1 through RARα/RXRα. Knockdown of BMP2 enhanced the induction of ATRA on the expression of COL X and MMP13, whereas overexpression of BMP2 abrogated this effectiveness. WNT4 might mediate the effects of ATRA and BMP2 on chondrocyte terminal differentiation. Dysregulation of BMP2 impaired the regulation of ATRA on WNT4 expression. Administration of ATRA to antler chondrocytes transfected with RUNX1 siRNA failed to induce the differentiation. Conversely, rRUNX1 strengthened the stimulation of ATRA on the expression of COL X and MMP13. Simultaneously, RUNX1 was a downstream effector of BMP2 and WNT4 in chondrocyte terminal differentiation. Moreover, WNT4 might play an important role in the crosstalk between BMP2 and RUNX1. Attenuation of BMP2 or WNT4 enhanced the interaction between ATRA and RUNX1, while constitutive expression of BMP2 or WNT4 reversed the regulation of ATRA on RUNX1. Collectively, WNT4 may act downstream of BMP2 to mediate the effects of ATRA on the terminal differentiation of antler chondrocytes through targeting RUNX1.
[Mh] Termos MeSH primário: Chifres de Veado/efeitos dos fármacos
Proteína Morfogenética Óssea 2/metabolismo
Diferenciação Celular/efeitos dos fármacos
Condrócitos/efeitos dos fármacos
Condrogênese/efeitos dos fármacos
Subunidade alfa 2 de Fator de Ligação ao Core/metabolismo
Tretinoína/farmacologia
Via de Sinalização Wnt/efeitos dos fármacos
Proteína Wnt4/metabolismo
[Mh] Termos MeSH secundário: Animais
Chifres de Veado/citologia
Chifres de Veado/metabolismo
Proteína Morfogenética Óssea 2/genética
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Condrócitos/metabolismo
Colágeno Tipo X/genética
Colágeno Tipo X/metabolismo
Subunidade alfa 2 de Fator de Ligação ao Core/genética
Cervos
Regulação da Expressão Gênica
Metaloproteinase 13 da Matriz/genética
Metaloproteinase 13 da Matriz/metabolismo
Interferência de RNA
Receptores do Ácido Retinoico/agonistas
Receptores do Ácido Retinoico/genética
Receptores do Ácido Retinoico/metabolismo
Ácido Retinoico 4 Hidroxilase/genética
Ácido Retinoico 4 Hidroxilase/metabolismo
Fatores de Tempo
Transfecção
Proteína Wnt4/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Bone Morphogenetic Protein 2); 0 (Collagen Type X); 0 (Core Binding Factor Alpha 2 Subunit); 0 (Receptors, Retinoic Acid); 0 (Wnt4 Protein); 5688UTC01R (Tretinoin); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase); EC 3.4.24.- (Matrix Metalloproteinase 13)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170425
[St] Status:MEDLINE
[do] DOI:10.1002/jcp.25972


  4 / 417 MEDLINE  
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[PMID]:28715412
[Au] Autor:El Shahawy M; Reibring CG; Neben CL; Hallberg K; Marangoni P; Harfe BD; Klein OD; Linde A; Gritli-Linde A
[Ad] Endereço:Department of Oral Biochemistry, Institute of Odontology, Sahlgrenska Academy at the University of Gothenburg, Göteborg, Sweden.
[Ti] Título:Cell fate specification in the lingual epithelium is controlled by antagonistic activities of Sonic hedgehog and retinoic acid.
[So] Source:PLoS Genet;13(7):e1006914, 2017 Jul.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The interaction between signaling pathways is a central question in the study of organogenesis. Using the developing murine tongue as a model, we uncovered unknown relationships between Sonic hedgehog (SHH) and retinoic acid (RA) signaling. Genetic loss of SHH signaling leads to enhanced RA activity subsequent to loss of SHH-dependent expression of Cyp26a1 and Cyp26c1. This causes a cell identity switch, prompting the epithelium of the tongue to form heterotopic minor salivary glands and to overproduce oversized taste buds. At developmental stages during which Wnt10b expression normally ceases and Shh becomes confined to taste bud cells, loss of SHH inputs causes the lingual epithelium to undergo an ectopic and anachronic expression of Shh and Wnt10b in the basal layer, specifying de novo taste placode induction. Surprisingly, in the absence of SHH signaling, lingual epithelial cells adopted a Merkel cell fate, but this was not caused by enhanced RA signaling. We show that RA promotes, whereas SHH, acting strictly within the lingual epithelium, inhibits taste placode and lingual gland formation by thwarting RA activity. These findings reveal key functions for SHH and RA in cell fate specification in the lingual epithelium and aid in deciphering the molecular mechanisms that assign cell identity.
[Mh] Termos MeSH primário: Diferenciação Celular/efeitos dos fármacos
Epitélio/efeitos dos fármacos
Proteínas Hedgehog/metabolismo
Tretinoína/farmacologia
[Mh] Termos MeSH secundário: Alelos
Animais
Linhagem Celular
Família 26 do Citocromo P450/genética
Família 26 do Citocromo P450/metabolismo
Células Epiteliais/metabolismo
Epitélio/crescimento & desenvolvimento
Feminino
Proteínas Hedgehog/genética
Masculino
Células de Merkel/efeitos dos fármacos
Células de Merkel/metabolismo
Camundongos
Ácido Retinoico 4 Hidroxilase/genética
Ácido Retinoico 4 Hidroxilase/metabolismo
Transdução de Sinais
Papilas Gustativas/metabolismo
Língua/crescimento & desenvolvimento
Proteínas Wnt/genética
Proteínas Wnt/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Hedgehog Proteins); 0 (Shh protein, mouse); 0 (Wnt Proteins); 0 (Wnt10b protein, mouse); 5688UTC01R (Tretinoin); EC 1.14.14.1 (Cyp26a1 protein, mouse); EC 1.14.14.1 (Cyp26c1 protein, mouse); EC 1.14.14.1 (Cytochrome P450 Family 26); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170824
[Lr] Data última revisão:
170824
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170718
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006914


  5 / 417 MEDLINE  
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[PMID]:28558289
[Au] Autor:Xiao Y; Jiang J; Hu W; Zhao Y; Hu J
[Ad] Endereço:MOE Laboratory for Earth Surface Processes, College of Urban and Environmental Sciences, Peking University, Beijing 100871, People's Republic of China.
[Ti] Título:Toxicity of triphenyltin on the development of retinal axons in zebrafish at low dose.
[So] Source:Aquat Toxicol;189:9-15, 2017 Aug.
[Is] ISSN:1879-1514
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The impacts of triphenyltin (TPT) on ecological health are of particular concern due to the unexpectedly high levels found in wild fish around the world. Here, zebrafish embryos were exposed to TPT via in ovo nano-injection to study its toxicity on the development of retinal axons in fish. Lipophilic dye labeling revealed obvious defects in retinal axon development in larvae with normally shaped eyes, with incidences of 0, 1.08%, 2.66%, 4.26%, and 6.85% observed in the control, 0.8, 4.0, 20.0, and 100ng TPT-Cl/g wet weight (ww) exposure groups, respectively, showing a dose-dependent increase. Since the lowest observable effective concentration of TPT to induce retinal axon development defects was 0.8ng TPT-Cl/g ww, which is lower than the concentrations in wild fish eggs, this defect would occur in wild fish larvae. Alterations in the expressions of pax6 and ephrinBs, which regulate the establishment of retinal polarity, were correlated with defect incidence. Expression levels of the CYP26A1 gene and protein were significantly up-regulated in all exposure groups compared with the control, which may lead to significant decreases in concentrations of all-trans retinoic acid (atRA). Such a disruption of RA metabolism would, at least partly, contribute to the incidence of developmental defects in retinal axons. This study is the first to report that TPT can interfere with development of retinal axons in fish at low dose.
[Mh] Termos MeSH primário: Axônios/efeitos dos fármacos
Desenvolvimento Embrionário/efeitos dos fármacos
Compostos Orgânicos de Estanho/toxicidade
Retina/efeitos dos fármacos
Poluentes Químicos da Água/toxicidade
Peixe-Zebra/embriologia
[Mh] Termos MeSH secundário: Animais
Relação Dose-Resposta a Droga
Embrião não Mamífero/anormalidades
Embrião não Mamífero/efeitos dos fármacos
Desenvolvimento Embrionário/genética
Larva/efeitos dos fármacos
Retina/anormalidades
Retina/embriologia
Ácido Retinoico 4 Hidroxilase/genética
Regulação para Cima
Peixe-Zebra/anormalidades
Peixe-Zebra/genética
Proteínas de Peixe-Zebra/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Organotin Compounds); 0 (Water Pollutants, Chemical); 0 (Zebrafish Proteins); 95T92AGN0V (triphenyltin); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase); EC 1.14.14.1 (cyp26a1 protein, zebrafish)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170531
[St] Status:MEDLINE


  6 / 417 MEDLINE  
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[PMID]:28281299
[Au] Autor:Khatri Y; Schifrin A; Bernhardt R
[Ad] Endereço:Institute of Biochemistry, Saarland University, Saarbrücken, Germany.
[Ti] Título:Investigating the effect of available redox protein ratios for the conversion of a steroid by a myxobacterial CYP260A1.
[So] Source:FEBS Lett;591(8):1126-1140, 2017 Apr.
[Is] ISSN:1873-3468
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Since cytochromes P450 are external monooxygenases, available surrogate redox partners have been used to reconstitute the P450 activity. However, the effect of various ratios of P450s and the redox proteins have not been extensively studied so far, although different combinations of the redox partners have shown variations in substrate conversion. To address this issue, CYP260A1 was reconstituted with various ratios of adrenodoxin and adrenodoxin reductase to convert 11-deoxycorticosterone, and the products were characterized by NMR. We show the effect of the available redox protein ratios not only on the P450 catalytic activity but also on the product pattern.
[Mh] Termos MeSH primário: Adrenodoxina/metabolismo
Proteínas de Bactérias/metabolismo
Desoxicorticosterona/metabolismo
Ferredoxina-NADP Redutase/metabolismo
Modelos Moleculares
Myxococcales/enzimologia
Ácido Retinoico 4 Hidroxilase/metabolismo
Esteroide Hidroxilases/metabolismo
[Mh] Termos MeSH secundário: Adrenodoxina/genética
Animais
Ácido Ascórbico/metabolismo
Proteínas de Bactérias/genética
Biocatálise
Catalase/metabolismo
Desoxicorticosterona/análogos & derivados
Desoxicorticosterona/química
Ferredoxina-NADP Redutase/genética
Depuradores de Radicais Livres/metabolismo
Peróxido de Hidrogênio/química
Espectroscopia de Ressonância Magnética
Estrutura Molecular
NADP/metabolismo
Oxirredução
Proteínas Recombinantes/metabolismo
Estereoisomerismo
Esteroide Hidroxilases/genética
Superóxido Dismutase/metabolismo
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (11-deoxycorticosterone-1-ene); 0 (Bacterial Proteins); 0 (Free Radical Scavengers); 0 (Recombinant Proteins); 12687-22-8 (Adrenodoxin); 40GP35YQ49 (Desoxycorticosterone); 53-59-8 (NADP); BBX060AN9V (Hydrogen Peroxide); EC 1.11.1.6 (Catalase); EC 1.14.- (Steroid Hydroxylases); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase); EC 1.15.1.1 (Superoxide Dismutase); EC 1.18.1.2 (Ferredoxin-NADP Reductase); PQ6CK8PD0R (Ascorbic Acid)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170311
[St] Status:MEDLINE
[do] DOI:10.1002/1873-3468.12619


  7 / 417 MEDLINE  
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[PMID]:28275201
[Au] Autor:Jing J; Nelson C; Paik J; Shirasaka Y; Amory JK; Isoherranen N
[Ad] Endereço:Department of Pharmaceutics (J.J., C.N., Y.S., N.I.), Department of Medicine (J.A.), and Department of Comparative Medicine (J.P.), University of Washington, Seattle, Washington.
[Ti] Título:Physiologically Based Pharmacokinetic Model of All- -Retinoic Acid with Application to Cancer Populations and Drug Interactions.
[So] Source:J Pharmacol Exp Ther;361(2):246-258, 2017 May.
[Is] ISSN:1521-0103
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:All- retinoic acid ( RA) is a front-line treatment of acute promyelocytic leukemia (APL). Due to its activity in regulating the cell cycle, it has also been evaluated for the treatment of other cancers. However, the efficacy of RA has been limited by RA inducing its own metabolism during therapy, resulting in a decrease of RA exposure during continuous dosing. Frequent relapse occurs in patients receiving RA monotherapy. In an attempt to combat therapy resistance, inhibitors of RA metabolism have been developed. Of these, ketoconazole and liarozole have shown some benefits, but their usage is limited by side effects and low potency toward the cytochrome P450 26A1 isoform (CYP26A1), the main RA hydroxylase. We determined the pharmacokinetic basis of therapy resistance to RA and tested whether the complex disposition kinetics of RA could be predicted in healthy subjects and in cancer patients in the presence and absence of inhibitors of RA metabolism using physiologically based pharmacokinetic (PBPK) modeling. A PBPK model of RA disposition was developed and verified in healthy individuals and in cancer patients. The population-based PBPK model of RA disposition incorporated saturable metabolic clearance of RA, induction of CYP26A1 by RA, and the absorption and distribution kinetics of RA. It accurately predicted the changes in RA exposure after continuous dosing and when coadministered with ketoconazole and liarozole. The developed model will be useful in interpretation of RA disposition and efficacy, design of novel dosing strategies, and development of next-generation RA metabolism inhibitors.
[Mh] Termos MeSH primário: Neoplasias
Ácido Retinoico 4 Hidroxilase/metabolismo
Tretinoína
[Mh] Termos MeSH secundário: Animais
Antineoplásicos/metabolismo
Antineoplásicos/farmacocinética
Biofarmácia/métodos
Desenho de Drogas
Interações Medicamentosas
Seres Humanos
Camundongos
Neoplasias/tratamento farmacológico
Neoplasias/metabolismo
Distribuição Tecidual
Tretinoína/metabolismo
Tretinoína/farmacocinética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 5688UTC01R (Tretinoin); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170310
[St] Status:MEDLINE
[do] DOI:10.1124/jpet.117.240523


  8 / 417 MEDLINE  
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[PMID]:28087565
[Au] Autor:Lee LM; Leung MB; Kwok RC; Leung YC; Wang CC; McCaffery PJ; Copp AJ; Shum AS
[Ad] Endereço:School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong.
[Ti] Título:Perturbation of Retinoid Homeostasis Increases Malformation Risk in Embryos Exposed to Pregestational Diabetes.
[So] Source:Diabetes;66(4):1041-1051, 2017 Apr.
[Is] ISSN:1939-327X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pregestational diabetes is highly associated with an increased risk of birth defects. However, factors that can increase or reduce the expressivity and penetrance of malformations in pregnancies in women with diabetes remain poorly identified. All- retinoic acid (RA) plays crucial roles in embryogenesis. Here, we find that , which encodes a key enzyme for catabolic inactivation of RA required for tight control of local RA concentrations, is significantly downregulated in embryos of diabetic mice. Embryonic tissues expressing show reduced efficiency of RA clearance. Embryos exposed to diabetes are thus sensitized to RA and more vulnerable to the deleterious effects of increased RA signaling. Susceptibility to RA teratogenesis is further potentiated in embryos with a preexisting genetic defect of RA metabolism. Increasing RA clearance efficiency using a preconditioning approach can counteract the increased susceptibility to RA teratogenesis in embryos of diabetic mice. Our findings provide new insight into gene-environment interactions that influence individual risk in the manifestation of diabetes-related birth defects and shed light on environmental risk factors and genetic variants for a stratified medicine approach to screening women with diabetes who are of childbearing age and assessing the risk of birth defects during pregnancy.
[Mh] Termos MeSH primário: Anormalidades Congênitas/metabolismo
Diabetes Mellitus Experimental/metabolismo
Gravidez em Diabéticas/metabolismo
Ácido Retinoico 4 Hidroxilase/genética
Tretinoína/metabolismo
[Mh] Termos MeSH secundário: Animais
Regulação para Baixo
Desenvolvimento Embrionário/genética
Feminino
Técnicas de Silenciamento de Genes
Interação Gene-Ambiente
Homeostase
Camundongos
Gravidez
Ácido Retinoico 4 Hidroxilase/metabolismo
Transdução de Sinais
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
5688UTC01R (Tretinoin); EC 1.14.14.1 (Cyp26a1 protein, mouse); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170115
[St] Status:MEDLINE
[do] DOI:10.2337/db15-1570


  9 / 417 MEDLINE  
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[PMID]:27860312
[Au] Autor:Meng CY; Li ZY; Fang WN; Song ZH; Yang DD; Li DD; Yang Y; Peng JP
[Ad] Endereço:State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
[Ti] Título:Cytochrome P450 26A1 modulates natural killer cells in mouse early pregnancy.
[So] Source:J Cell Mol Med;21(4):697-710, 2017 Apr.
[Is] ISSN:1582-4934
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Cytochrome P450 26A1 (CYP26A1) has a spatiotemporal expression pattern in the uterus, with a significant increase in mRNA and protein levels during peri-implantation. Inhibiting the function or expression of CYP26A1 can cause pregnancy failure, suggesting an important regulatory role of CYP26A1 in the maintenance of pregnancy. However, little is known about the exact mechanism involved. In this study, using a pCR3.1-cyp26a1 plasmid immunization mouse model and a Cyp26a1-MO (Cyp26a1-specific antisense oligos) knockdown mouse model, we report that the number of Dolichos biflorus agglutinin (DBA) lectin-positive uterine natural killer (uNK) cells was reduced in pCR3.1-cyp26a1 plasmid immunized and Cyp26a1-MO-treated mice. In contrast, the percentage of CD3 CD49b NK cells in the uteri from the treatment group was significantly higher than that of the control group in both models. Similarly, significantly up-regulated expression of CD49b (a pan-NK cell marker), interferon gamma, CCL2, CCR2 (CCL2 receptor) and CCL3 were detected in the uteri of pCR3.1-cyp26a1- and Cyp26a1-MO-treated mice. Transcriptome analysis suggested that CYP26A1 might regulate NK cells through chemokines. In conclusion, the present data suggest that silencing CYP26A1 expression/function can decrease the number of uNK cells and significantly increase the percentage of CD3 CD49b NK cells in the uteri of pregnant mice. These findings provide a new line of evidence correlating the deleterious effects of blocking CYP26A1 in pregnancy with the aberrant regulation of NK cells in the uterus.
[Mh] Termos MeSH primário: Células Matadoras Naturais/enzimologia
Ácido Retinoico 4 Hidroxilase/metabolismo
[Mh] Termos MeSH secundário: Animais
Anticorpos/imunologia
Contagem de Células
Quimiocinas/metabolismo
Feminino
Perfilação da Expressão Gênica
Técnicas de Silenciamento de Genes
Imunização
Células Matadoras Naturais/efeitos dos fármacos
Masculino
Camundongos Endogâmicos BALB C
Modelos Animais
Morfolinos/farmacologia
Plasmídeos/metabolismo
Gravidez
Reprodutibilidade dos Testes
Útero/citologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies); 0 (Chemokines); 0 (Morpholinos); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161119
[St] Status:MEDLINE
[do] DOI:10.1111/jcmm.13013


  10 / 417 MEDLINE  
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[PMID]:27904043
[Au] Autor:Ochiai W; Hirose A; Kawamura T; Komachi K; Yamamoto Y; Kitaoka S; Hatogai J; Kusunoki Y; Kon R; Ikarashi N; Sugiyama K
[Ad] Endereço:Department of Clinical Pharmacokinetics, School of Pharmacy and Pharmaceutical Sciences, Hoshi University.
[Ti] Título:Role of the Drug-Metabolizing Enzyme CYP during Mouse Liver Development.
[So] Source:Biol Pharm Bull;39(12):2015-2021, 2016.
[Is] ISSN:1347-5215
[Cp] País de publicação:Japan
[La] Idioma:eng
[Ab] Resumo:The drug-metabolizing enzyme CYP is mainly involved in the metabolism of various substances in the liver, such as drugs, endogenous substances, and carcinogens. Recent reports have also revealed that CYP1B1 plays a major role in the developmental process. Because the level of CYP expression is markedly high in the liver, we hypothesize that CYP plays a role in the developmental process of the liver. To verify this hypothesis, we analyzed the expression patterns of various CYP molecular species and their functions during the differentiation of embryonic stem cells (ES cells) into hepatocytes and the developmental process in mice. The results demonstrated that CYP2R1 and CYP26A1 are expressed at an earlier stage of the differentiation of ES cells into hepatocytes than hepatoblast-specific markers. Additionally, during the development of the mouse liver, CYP2R1 and CYP26A1 were mostly up-regulated during the stage when hepatoblasts appeared. In addition, when CYP2R1 and CYP26A1 expressions were forced in ES cells and liver of adult mice, they differentiated into hepatoblast marker positive cells. These results suggest that CYP2R1 and CYP26A1 may play a major role in hepatoblast cell differentiation during the development of the liver.
[Mh] Termos MeSH primário: Colestanotriol 26-Mono-Oxigenase/metabolismo
Fígado/embriologia
Fígado/enzimologia
Ácido Retinoico 4 Hidroxilase/metabolismo
[Mh] Termos MeSH secundário: Animais
Diferenciação Celular
Colestanotriol 26-Mono-Oxigenase/genética
DNA
Células-Tronco Embrionárias/citologia
Células-Tronco Embrionárias/enzimologia
Feminino
Hepatócitos/enzimologia
Peptídeos e Proteínas de Sinalização Intercelular/metabolismo
Camundongos Endogâmicos ICR
Preparações Farmacêuticas/metabolismo
Plasmídeos
Gravidez
Ácido Retinoico 4 Hidroxilase/genética
Transfecção
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Dlk1 protein, mouse); 0 (Intercellular Signaling Peptides and Proteins); 0 (Pharmaceutical Preparations); 9007-49-2 (DNA); EC 1.14.14.1 (Cyp26a1 protein, mouse); EC 1.14.14.1 (Retinoic Acid 4-Hydroxylase); EC 1.14.14.24 (Cyp2r1 protein, mouse); EC 1.14.15.15 (Cholestanetriol 26-Monooxygenase)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:170119
[Lr] Data última revisão:
170119
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161202
[St] Status:MEDLINE



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