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https://www.readbyqxmd.com/read/28743050/pml-rar%C3%AE-stabilized-by-zinc-in-human-acute-promyelocytic-leukemia-nb4-cells
#1
Bo Zhu, Jia-Yu Wang, Jun-Jie Zhou, Feng Zhou, Wei Cheng, Ying-Ting Liu, Jie Wang, Xiao Chen, Dian-Hua Chen, Lan Luo, Zi-Chun Hua
Acute promyelocytic leukemia (APL) is characterized and driven by the promyelocytic leukemia protein-retinoic acid receptor alpha (PML-RARα) fusion gene. Previous studies have highlighted the importance of PML-RARα degradation in the treatment against APL. Considering the presence of two zinc fingers in the PML-RARα fusion protein, we explored the function of zinc homeostasis in maintaining PML-RARα stability. We demonstrated for the first time that zinc depletion by its chelator N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) triggered PML-RARα degradation in NB4 APL cells via the proteasome pathway rather than the autophagy-lysosomal pathway...
July 19, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28741179/activation-of-liver-x-receptor-inhibits-oct2-mediated-organic-cation-transport-in-renal-proximal-tubular-cells
#2
Teerasak Wongwan, Suticha Kittayaruksakul, Nithi Asavapanumas, Varanuj Chatsudthipong, Sunhapas Soodvilai
Liver X receptor (LXR) is transcriptional factor that plays an important role in the regulation of energy metabolism such as cholesterol, lipid, and glucose metabolism as well as membrane transporters and channels. Using both in vitro and in vivo models, LXR regulation of the expression and function of renal organic cation transporter 2 (OCT2) was observed. Synthetic LXR agonist (GW3965) and endogenous LXR agonist (22R-hydroxycholesterol) significantly reduced the uptake of (3)H-MPP(+), a prototypic substrate of OCT2, in both OCT2- Chinese hamster ovary K1 and human renal proximal tubular cells (RPTEC/TERT1)...
July 25, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28739660/a-gene-implicated-in-activation-of-retinoic-acid-receptor-targets-is-a-novel-renal-agenesis-gene-in-humans
#3
Patrick D Brophy, Maria Rasmussen, Mrutyunjaya Parida, Greg Bonde, Benjamin W Darbro, Xiaojing Hong, Jason C Clarke, Kevin A Peterson, James Denegre, Michael Schneider, Caroline R Sussman, Lone Sunde, Dorte L Lildballe, Jens Michael Hertz, Robert A Cornell, Stephen A Murray, John R Manak
Renal agenesis (RA) is one of the more extreme examples of congenital anomalies of the kidney and urinary tract (CAKUT). Bilateral renal agenesis is almost invariably fatal at birth, and unilateral renal agenesis can lead to future health issues including end stage renal disease. Genetic investigations have identified several gene variants which cause RA, including EYA1, LHX1, and WT1 However, whereas compound null mutations of genes encoding α and γ retinoic acid receptors (RARs) cause RA in mice, to date there have been no reports of variants in RAR genes causing RA in humans...
July 24, 2017: Genetics
https://www.readbyqxmd.com/read/28738907/rig-i-expression-in-perifascicular-myofibers-is-a-reliable-biomarker-of-dermatomyositis
#4
Xavier Suárez-Calvet, Eduard Gallardo, Iago Pinal-Fernandez, Noemi De Luna, Cinta Lleixà, Jordi Díaz-Manera, Ricardo Rojas-García, Ivan Castellví, M Angeles Martínez, Josep M Grau, Albert Selva-O'Callaghan, Isabel Illa
BACKGROUND: Dermatomyositis (DM) is inflammatory myopathy or myositis characterized by muscle weakness and skin manifestations. In the differential diagnosis of DM the evaluation of the muscle biopsy is of importance among other parameters. Perifascicular atrophy in the muscle biopsy is considered a hallmark of DM. However, perifascicular atrophy is not observed in all patients with DM and, conversely, perifascicular atrophy can be observed in other myositis such as antisynthetase syndrome (ASS), complicating DM diagnosis...
July 24, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28738533/mir-200a-expression-in-cd4-t-cells-correlates-with-the-expression-of-th17-treg-cells-and-relevant-cytokines-in-psoriasis-vulgaris-a-case-control-study
#5
Xiao-Yan Wang, Xing-Yu Chen, Jun Li, Hong-Ying Zhang, Juan Liu, Le-Dong Sun
The main aim of this study is to investigate the underlying relationship shared between microRNA-200a (miR-200a) and its link to concentrations of Th17 and Treg cells, mRNA expressions of their specific transcription factors retinoic acid-related orphan receptor γt (RORγt) and head box protein 3 (FOXP3) and relevant cytokines in patients with psoriasis vulgaris (PV). A total of 189 patients previously diagnosed with PV were selected as the experimental group, whilst 109 healthy individuals as the control group...
July 20, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28736154/retinoic-acid-induces-differentiation-of-buffalo-bubalus-bubalis-embryonic-stem-cells-into-germ-cells
#6
Syed Mohmad Shah, Suresh Kumar Singla, Prabhat Palta, Radhey Sham Manik, Manmohan Singh Chauhan
Development of precise and reproducible culture system for in vitro differentiation of embryonic stem (ES) cells into germ cells counts as a major leap forward for understanding not only the remarkable process of gametogenesis, otherwise obscured by limited availability of precursor primordial germ cells (PGCs), but in finally treating the catastrophic infertility. Taking into account the significant role of retinoic acid (RA) during in vivo gametogenesis, we designed the present study to investigate the effects of its stimulation on directing the differentiation of ES cells into germ cells...
July 19, 2017: Gene
https://www.readbyqxmd.com/read/28735889/acute-promyelocytic-leukemia-a-perspective
#7
Farhad Ravandi, Richard Stone
Treatment of patients with acute promyelocytic leukemia has significantly improved with the introduction of target specific agents all-trans retinoic acid (ATRA) and arsenic trioxide (ATO) with long term survival a reality for the majority of patients. This can serve as a paradigm for cancer therapy where with the introduction of more potent target-specific drugs our reliance on the traditional cytotoxic agents is likely to diminish and less toxic and more effective regimens are likely to replace the current intensive chemotherapy regimens...
July 6, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28735443/retinoic-acid-regulates-avian-lung-branching-through-a-molecular-network
#8
Hugo Fernandes-Silva, Patrícia Vaz-Cunha, Violina Baranauskaite Barbosa, Carla Silva-Gonçalves, Jorge Correia-Pinto, Rute Silva Moura
Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development...
July 22, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28735239/effects-of-a-glyphosate-based-herbicide-in-pejerrey-odontesthes-humensis-embryonic-development
#9
Yuri Dornelles Zebral, Patrícia Gomes Costa, Bruna de Castro Knopp, Luize Real Lansini, Bruna Zafalon-Silva, Adalto Bianchini, Ricardo Berteaux Robaldo
Glyphosate-based herbicides (GBH) are the major pesticides used worldwide. Among them, the Roundup formulations are the most popular. Some aspects of GBH toxicity are well known, such as induction of oxidative stress. However, embryotoxicity is scarcely known. Therefore, the aim of the present study was to evaluate the effect of exposure to different Roundup Transorb R concentrations (0.36, 1.80, 3.62 and 5.43 mg glyphosate a.e./L) on Odontesthes humensis embryonic development. Embryos were sampled at three exposure times (48, 72 and 96 h)...
July 17, 2017: Chemosphere
https://www.readbyqxmd.com/read/28734946/impaired-rhodopsin-generation-in-the-rat-model-of-diabetic-retinopathy
#10
Volha V Malechka, Gennadiy Moiseyev, Yusuke Takahashi, Younghwa Shin, Jian-Xing Ma
Diabetic retinopathy is a common complication of diabetes mellitus. Diabetic patients experience functional deficits in dark adaptation, contrast sensitivity, and color perception before microvascular pathologies become apparent. Here, we evaluated early changes in neural retinal function and in retinoid metabolism in the eye in diabetes. Streptozotocin-induced diabetic rats showed decreased a-wave and b-wave amplitudes of scotopic and photopic electroretinography responses four months after diabetes induction compared to nondiabetic controls...
July 19, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28733465/the-retinol-binding-protein-receptor-stra6-regulates-diurnal-insulin-responses
#11
Christy M Gliniak, J Mark Brown, Noa Noy
It has long been appreciated that insulin action is closely tied to circadian rhythms. However, mechanisms that dictate diurnal insulin sensitivity in metabolic tissues are not well understood. Retinol binding protein 4 (RBP4) has been implicated as a driver of insulin resistance in rodents and humans, and has become an attractive drug target in type 2 diabetes. RBP4 is synthesized primarily in the liver where it binds retinol and transports it to tissues throughout the body. The retinol-RBP4 complex (holo-RBP) can be recognized by a cell surface receptor known as stimulated by retinoic acid 6 (STRA6) which transports retinol into cells...
July 21, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28732729/crystal-structures-of-an-atypical-aldehyde-dehydrogenase-having-bidirectional-oxidizing-and-reducing-activities
#12
Kyoungho Jung, Seung-Hye Hong, Ho-Phuong-Thuy Ngo, Thien-Hoang Ho, Yeh-Jin Ahn, Deok-Kun Oh, Lin-Woo Kang
Aldehyde dehydrogenases (ALDHs) are NAD(P)(+)-dependent oxidoreductases that catalyze the oxidation of a variety of aldehydes to their acid forms. In this study, we determined the crystal structures of ALDH from Bacillus cereus (BcALDH), alone, and in complex with NAD(+) and NADP(+). This enzyme can oxidize all-trans-retinal to all-trans-retinoic acid using either NAD(+) or NADP(+) with equal efficiency, and atypically, as a minor activity, can reduce all-trans-retinal to all-trans-retinol using NADPH. BcALDH accommodated the additional 2'-phosphate of NADP(+) by expanding the cofactor-binding pocket and upshifting the AMP moiety in NADP(+)...
July 18, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28732066/inhibition-of-pulmonary-%C3%AE-carotene-15-15-oxygenase-expression-by-glucocorticoid-involves-ppar%C3%AE
#13
Xiaoming Gong, Raju Marisiddaiah, Lewis P Rubin
β-carotene 15,15'-oxygenase (BCO1) catalyzes the first step in the conversion of dietary provitamin A carotenoids to vitamin A. This enzyme is expressed in a variety of developing and adult tissues, suggesting that its activity may regulate local retinoid synthesis. Vitamin A and related compounds (retinoids) are critical regulators of lung epithelial development, integrity, and injury repair. A balance between the actions of retinoids and glucocorticoids (GCs) promotes normal lung development and, in particular, alveolarization...
2017: PloS One
https://www.readbyqxmd.com/read/28729840/cardiac-subtype-specific-modeling-of-kv1-5-ion-channel-deficiency-using-human-pluripotent-stem-cells
#14
Maike Marczenke, Ilaria Piccini, Isabella Mengarelli, Jakob Fell, Albrecht Röpke, Guiscard Seebohm, Arie O Verkerk, Boris Greber
The ultrarapid delayed rectifier K(+) current (IKur), mediated by Kv1.5 channels, constitutes a key component of the atrial action potential. Functional mutations in the underlying KCNA5 gene have been shown to cause hereditary forms of atrial fibrillation (AF). Here, we combine targeted genetic engineering with cardiac subtype-specific differentiation of human induced pluripotent stem cells (hiPSCs) to explore the role of Kv1.5 in atrial hiPSC-cardiomyocytes. CRISPR/Cas9-mediated mutagenesis of integration-free hiPSCs was employed to generate a functional KCNA5 knockout...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28729405/super-enhancer-analysis-defines-novel-epigenomic-subtypes-of-non-apl-aml-including-an-rar%C3%AE-dependency-targetable-by-sy-1425-a-potent-and-selective-rar%C3%AE-agonist
#15
Michael R McKeown, M Ryan Corces, Matthew L Eaton, Chris Fiore, Emily Lee, Jeremy T Lopez, Mei Wei Chen, Darren Smith, Steven M Chan, Julie L Koenig, Kathryn Austgen, Matt G Guenther, David A Orlando, Jakob Lovén, Christian C Fritz, Ravindra Majeti
We characterized the enhancer landscape of 66 AML patients, identifying 6 novel subgroups and their associated regulatory loci. These subgroups are defined by their super-enhancer (SE) maps, orthogonal to somatic mutations, and are associated with distinct leukemic cell states. Examination of transcriptional drivers for these epigenomic subtypes uncovers a subset of patients with a particularly strong super-enhancer at the retinoic acid receptor alpha (RARA) gene locus. Presence of a RARA SE and concomitant high levels of RARA mRNA predisposes cell lines and ex vivo models to exquisite sensitivity to a selective agonist of RARα, SY-1425 (tamibarotene)...
July 20, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28727051/carotenoid-intake-and-scd-genotype-exert-complementary-effects-over-fat-content-and-fatty-acid-composition-in-duroc-pigs
#16
E Henriquez-Rodriguez, R N Pena, A R Seradj, L Fraile, P Christou, M Tor, J Estany
Nutritional and genetic strategies are needed to enhance intramuscular fat (IMF) and MUFA content without altering carcass leanness. Dietary vitamin A restriction has been suggested to specifically promote IMF, whereas a polymorphism of the () gene has shown to specifically increase MUFA. The purpose of this study was to investigate the combined effects of provitamin A (PVA) carotenoid intake and genotype (>) on hepatic retinoid content and on the liver, muscle (LM and gluteus medius [GM]), and subcutaneous fat (SF) content and fatty acid composition...
June 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28724938/a-novel-role-for-rar%C3%AE-agonists-as-apolipoprotein-ciii-inhibitors-identified-from-high-throughput-screening
#17
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/28720593/vitamin-a-endocrine-tissues-and-hormones-interplay-and-interactions
#18
Julie Brossaud, Veronique Pallet, Jean-Benoit Corcuff
Vitamin A (retinol) is a micronutrient critical for cell proliferation and differentiation. In adults, vitamin A and metabolites such as retinoic acid (RA) play major roles in vision, immune and brain functions, and tissue remodelling and metabolism. This review presents the physiological interactions of retinoids and endocrine tissues and hormonal systems. Two endocrine systems have been particularly studied. In the pituitary, retinoids targets the corticotrophs with a possible therapeutic use in corticotropinomas...
July 18, 2017: Endocrine Connections
https://www.readbyqxmd.com/read/28718514/aldehyde-dehydrogenase-1-a1-regulates-energy-metabolism-in-adipocytes-from-different-species
#19
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/28718066/the-preventive-effects-of-taurine-on-neural-tube-defects-through-the-wnt-pcp-jnk-dependent-pathway
#20
Qinghua Zhang, Yang Liu, Hui Wang, Li Ma, Hechun Xia, Jianguo Niu, Tao Sun, Li Zhang
The aim of this study was to clarify the protective role of taurine in neuronal apoptosis and the role of the Wnt/PCP-Jnk pathway in mediating the preventive effects of taurine on neural tube defects (NTDs). HT-22 cells (a hippocampal neuron cell line) were divided into a control group, a glutamate-induced apoptosis group, and glutamate (4.0 mmol/L) plus low-dose taurine (L; 0.5 mmol/L) and high-dose taurine (H; 2.0 mmol/L) groups. The MTT assay was used to monitor cell proliferation and cell survival. Immunofluorescence and Western blot analyses were used to determine caspase 9 expression...
July 17, 2017: Amino Acids
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