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https://www.readbyqxmd.com/read/29351577/effects-of-excess-thromboxane-a2-on-placental-development-and-nutrient-transporters-in-a-mus-musculus-model-of-fetal-growth-restriction
#1
Karen J Gibbins, Katherine N Gibson-Corley, Ashley S Brown, Matthew Wieben, Richard C Law, Camille M Fung
Hypertensive disease of pregnancy (HDP) with placental insufficiency is the most common cause of fetal growth restriction (FGR) in the developed world. Despite the known negative consequences of HDP both to the mother and fetus, little is known about the longitudinal placental changes that occur as HDP progresses in pregnancy. This is because longitudinal sampling of human placentae during each gestation is impossible. Therefore, using a mouse model of thromboxane A2-analog infusion to mimic human HDP in the last trimester, we calculated placental efficiencies based on fetal and placental weights, quantified spongiotrophoblast and labyrinth thicknesses and vascular density within these layers, examined whether hypoxia signaling pathway involving vascular endothelial growth factor A (VEGFA) and its receptors (VEGFR1, VEGFR2) and matrix metalloproteinases (MMPs) contributed to vascular change, and examined nutrient transporter abundance including glucose transporters 1 and 3 (GLUT1, GLUT3), neutral amino acid transporters 1, 2, and 4 (SNAT1, SNAT2, and SNAT4), fatty acid transporters 2 and 4 (FATP2, FATP4) and fatty acid translocase (CD36) from embryonic day 15...
January 17, 2018: Biology of Reproduction
https://www.readbyqxmd.com/read/29341887/molecular-basis-of-substrate-polyspecificity-of-the-candida-albicans-mdr1p-multidrug-h-antiporter
#2
Archana Kumari Redhu, Atanu Banerjee, Abdul Haseeb Shah, Alexis Moreno, Manpreet Kaur Rawal, Remya Nair, Pierre Falson, Rajendra Prasad
The molecular basis of polyspecificity of Mdr1p, a major drug/H+ antiporter of Candida albicans, is not elucidated. We have probed the nature of the drug-binding pocket by performing systematic mutagenesis of the 12 transmembrane segments. Replacement of the 252 amino acid residues with alanine or glycine yielded 2/3 neutral mutations while 1/3 led to the complete or selective lost of resistance to drugs or substrates transported by the pump. Using the GlpT-based 3D-model of Mdr1p, we roughly categorized these critical residues depending on their type and localization 1°/ main structural impact ("S" group), 2°/ exposure to the lipid interface ("L" group), 3°/ buried but not facing the main central pocket, inferred as critical for the overall H+/drug antiport mechanism ("M" group) and finally 4°/ buried and facing the main central pocket ("B" group)...
January 13, 2018: Journal of Molecular Biology
https://www.readbyqxmd.com/read/29340834/limited-daily-feeding-and-intermittent-feeding-have-different-effects-on-regional-brain-energy-homeostasis-during-aging
#3
Kosara Smiljanic, Smilja Todorovic, Aleksandra Mladenovic Djordjevic, Tim Vanmierlo, Dieter Lütjohann, Sanja Ivkovic, Selma Kanazir
Albeit aging is an inevitable process, the rate of aging is susceptible to modifications. Dietary restriction (DR) is a vigorous nongenetic and nonpharmacological intervention that is known to delay aging and increase healthspan in diverse species. This study aimed to compare the impact of different restricting feeding regimes such as limited daily feeding (LDF, 60% AL) and intermittent feeding (IF) on brain energy homeostasis during aging. The analysis was focused on the key molecules in glucose and cholesterol metabolism in the cortex and hippocampus of middle-aged (12-month-old) and aged (24-month-old) male Wistar rats...
January 16, 2018: Biogerontology
https://www.readbyqxmd.com/read/29335581/role-of-hypoxia-in-diffuse-large-b-cell-lymphoma-metabolic-repression-and-selective-translation-of-hk2-facilitates-development-of-dlbcl
#4
Kavita Bhalla, Sausan Jaber, Nanaji Nahid M, Karen Underwood, Afshin Beheshti, Ari Landon, Binny Bhandary, Paul Bastain, Andrew M Evens, John Haley, Brian Polster, Ronald B Gartenhaus
Published molecular profiling studies in patients with lymphoma suggested the influence of hypoxia inducible factor-1 alpha (HIF1α) targets in prognosis of DLBCL. Yet, the role of hypoxia in hematological malignancies remains unclear. We observed that activation of HIF1α resulted in global translation repression during hypoxic stress in DLBCL. Protein translation efficiency as measured using 35S-labeled methionine incorporation revealed a ≥50% reduction in translation upon activation of HIF1α. Importantly, translation was not completely inhibited and expression of clinically correlated hypoxia targets such as GLUT1, HK2, and CYT-C was found to be refractory to translational repression under hypoxia in DLBCL cells...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29330287/targeted-akt-inhibition-in-prostate-cancer-cells-and-spheroids-reduces-aerobic-glycolysis-and-generation-of-hyperpolarized-1-13c-lactate
#5
Sui Seng Tee, Izabela Suster, Steven Truong, Sangmoo Jeong, Roozbeh Eskandari, Valentina Di Gialleonardo, Julio A Alvarez, Hannah N Aldeborgh, Kayvan Keshari
The PI3K/AKT/mTOR (PAM) signaling pathway is frequently mutated in prostate cancer. Specific AKT inhibitors are now in advanced clinical trials and this study investigates the effect of MK2206, a non-ATP competitive inhibitor, on the cellular metabolism in the context of prostate cancer. A significant reduction in cell motility and aerobic glycolysis was observed in prostate cancer cells with treatment. These changes were not accompanied by a reduction in the ratio of high-energy phosphates or a change in total protein levels of enzymes (e...
January 12, 2018: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/29306089/phenotype-variability-of-glut1-deficiency-syndrome-description-of-a-case-series-with-novel-slc2a1-gene-mutations
#6
Lidia Di Vito, Laura Licchetta, Tommaso Pippucci, Sara Baldassari, Carlotta Stipa, Barbara Mostacci, Lara Alvisi, Paolo Tinuper, Francesca Bisulli
No abstract text is available yet for this article.
January 3, 2018: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/29303961/individualizing-treatment-approaches-for-epileptic-patients-with-glucose-transporter-type1-glut-1-deficiency
#7
REVIEW
Armond Daci, Adnan Bozalija, Fisnik Jashari, Shaip Krasniqi
Monogenic and polygenic mutations are important contributors in patients suffering from epilepsy, including metabolic epilepsies which are inborn errors of metabolism with a good respond to specific dietetic treatments. Heterozygous variation in solute carrier family 2, facilitated glucose transporter member 1 (SLC2A1) and mutations of the GLUT1/SLC2A2 gene results in the failure of glucose transport, which is related with a glucose type-1 transporter (GLUT1) deficiency syndrome (GLUT1DS). GLUT1 deficiency syndrome is a treatable disorder of glucose transport into the brain caused by a variety of mutations in the SLC2A1 gene which are the cause of different neurological disorders also with different types of epilepsy and related clinical phenotypes...
January 5, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29301589/linking-foxo3-ncoa3-and-tcf7l2-to-ras-pathway-phenotypes-through-a-genome-wide-forward-genetic-screen-in-human-colorectal-cancer-cells
#8
Snehangshu Kundu, Muhammad Akhtar Ali, Niklas Handin, Narendra Padhan, Jimmy Larsson, Maria Karoutsou, Kenneth Ban, Jacek R Wiśniewski, Per Artursson, Liqun He, Mats Hellström, Tobias Sjöblom
BACKGROUND: The Ras pathway genes KRAS, BRAF, or ERBBs have somatic mutations in ~ 60% of human colorectal carcinomas. At present, it is unknown whether the remaining cases lack mutations activating the Ras pathway or whether they have acquired mutations in genes hitherto unknown to belong to the pathway. METHODS: To address the second possibility and extend the compendium of Ras pathway genes, we used genome-wide transposon mutagenesis of two human colorectal cancer cell systems deprived of their activating KRAS or BRAF allele to identify genes enabling growth in low glucose, a Ras pathway phenotype, when targeted...
January 4, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29300939/cgmp-pkg-i-pathway-mediated-glut1-4-regulation-by-no-nitric-oxide-in-female-rat-granulosa-cells
#9
Ye Tian, Dai Heng, Kaili Xu, Wenbo Liu, Xuechun Weng, Xusong Hu, Cheng Zhang
Nitric oxide (NO) is a multifunctional gaseous molecule that plays important roles in mammalian reproductive functions including follicular growth and development. Although our previous study showed that NO mediated 3,5,3'-triiodothyronine (T3) and follicle-stimulating hormone (FSH)-induced granulosa cell development via upregulation of GLUT1 (glucose transporter protein ) and GLUT4 in granulosa cells, little is known about the precise mechanisms regulating ovarian development via glucose. The objective of the present study was to determine the cellular and molecular mechanism by which NO regulates GLUT expression and glucose uptake in granulosa cells...
December 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/29299135/acquired-resistance-to-pi3k-mtor-inhibition-is-associated-with-mitochondrial-dna-mutation-and-glycolysis
#10
King Xin Koh, Gim Hwa Tan, Sarah Hong Hui Low, Mohd Feroz Mohd Omar, Min Ji Han, Barry Iacopetta, Ross Soo, Mounia Beloueche-Babari, Bhaskar Bhattacharya, Richie Soong
Acquired resistance (AQR) to drug treatment occurs frequently in cancer patients and remains an impediment to successful therapy. The aim of this study was to gain insight into how AQR arises following the application of PI3K/mTOR inhibitors. H1975 lung cancer cells with EGFR T790M mutations that confer resistance to EGFR inhibitors underwent prolonged treatment with the PI3K/mTOR inhibitor, BEZ235. Monoclonal cells with stable and increased resistance to BEZ235 were obtained after 8 months treatment. These AQR clones showed class-specific resistance to PI3K/mTOR inhibitors, reduced G1 cell cycle arrest and impedance of migration following PI3K/mTOR inhibition, reduced PTEN expression and increased Akt and S6RP phosphorylation...
December 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/29295858/hif-1%C3%AE-stabilization-reduces-retinal-degeneration-in-a-mouse-model-of-retinitis-pigmentosa
#11
Lorena Olivares-González, Cristina Martínez-Fernández de la Cámara, David Hervás, José María Millán, Regina Rodrigo
Retinitis pigmentosa (RP) is a group of inherited retinal dystrophies characterized by progressive and irreversible loss of vision due to rod and cone degeneration. Evidence suggests that an inappropriate oxygen level could contribute to its pathogenesis. Rod cell death could increase oxygen concentration, reduce hypoxia-inducible factor 1 (HIF-1α) and contribute to cone cell death. The purposes of this study were: 1) to analyze the temporal profile of HIF-1α, its downstream effectors VEGF, endothelin-1 (ET-1), iNOS, and glucose transporter 1 (GLUT1), and neuroinflammation in retinas of the murine model of rd10 (retinal degeneration 10) mice with RP; 2) to study oxygen bioavailability in these retinas; and 3) to investigate how stabilizing HIF-1α proteins with dimethyloxaloglycine (DMOG), a prolyl hydroxylase inhibitor, affects retinal degeneration, neuroinflammation, and antioxidant response in rd10 mice...
January 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29282992/enhanced-anti-hepatocarcinoma-efficacy-by-glut1-targeting-and-cellular-microenvironment-responsive-pamam-camptothecin-conjugate
#12
Pengkai Ma, Yi Sun, Jianhua Chen, Hongpin Li, Hongyu Zhu, Xing Gao, Xinning Bi, Yujie Zhang
The efficient targeting of drugs to tumor cell and subsequent rapid drug release remain primary challenges in the development of nanomedicines for cancer therapy. Here, we constructed a glucose transporter 1 (GLUT1)-targeting and tumor cell microenvironment-sensitive drug release Glucose-PEG-PAMAM-s-s-Camptothecin-Cy7 (GPCC) conjugate to tackle the dilemma. The conjugate was characterized by a small particle size, spherical shape, and glutathione (GSH)-sensitive drug release. In vitro tumor targeting was explored in monolayer (2D) and multilayer tumor spheroid (3D) HepG2 cancer cell models (GLUT1+)...
November 2018: Drug Delivery
https://www.readbyqxmd.com/read/29235571/the-hypoxia-marker-caix-is-prognostic-in-the-uk-phase-iii-vortex-biobank-cohort-an-important-resource-for-translational-research-in-soft-tissue-sarcoma
#13
Laura Forker, Piers Gaunt, Stefano Sioletic, Patrick Shenjere, Robert Potter, Darren Roberts, Joely Irlam, Helen Valentine, David Hughes, Ana Hughes, Lucinda Billingham, Rob Grimer, Beatrice Seddon, Ananya Choudhury, Martin Robinson, Catharine M L West
BACKGROUND: Despite high metastasis rates, adjuvant/neoadjuvant systemic therapy for localised soft tissue sarcoma (STS) is not used routinely. Progress requires tailoring therapy to features of tumour biology, which need exploration in well-documented cohorts. Hypoxia has been linked to metastasis in STS and is targetable. This study evaluated hypoxia prognostic markers in the phase III adjuvant radiotherapy VorteX trial. METHODS: Formalin-fixed paraffin-embedded tumour biopsies, fresh tumour/normal tissue and blood were collected before radiotherapy...
December 12, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/29225472/18f-fluorodeoxyglucose-uptake-predicts-met-expression-in-lung-adenocarcinoma
#14
Shuxian An, Xiang Zhou, Jianjun Liu, Gang Huang
Objective: MET is a member of the receptor tyrosine kinases. Several MET-targeting inhibitors and antagonistic antibodies have shown promising data in clinical trials of lung adenocarcinoma. Finding noninvasive diagnostic tools to estimate the status of MET is helpful in clinical practice. 18F-fluorodeoxyglucose positron emission tomography/computerized tomography (18F-FDG PET/CT) has been used routinely for the diagnosis and staging of tumors. However, the relationship between MET expression and 18F-FDG uptake has not been investigated yet...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29223885/three-novel-slc2a1-mutations-in-bulgarian-patients-with-different-forms-of-genetic-generalized-epilepsy-reflecting-the-clinical-and-genetic-diversity-of-glut1-deficiency-sydnrome
#15
Nevyana Ivanova, Valentina Peycheva, Kunka Kamenarova, Dalia Kancheva, Irina Tsekova, Iliana Aleksandrova, Dimitrina Hristova, Ivan Litvinenko, Diana Todorova, Gergana Sarailieva, Petya Dimova, Veselin Tomov, Veneta Bozhinova, Vanio Mitev, Radka Kaneva, Albena Jordanova
PURPOSE: GLUT1-deficiency syndrome (GLUT1-DS) is a metabolic brain disorder with a great clinical heterogeneity underlined by various mutations in the SLC2A1 gene which make the clinical and genetic diagnosis complicated. The purpose of our study is to investigate the genetic defects affecting the SLC2A1 gene in a group of Bulgarian patients with genetic generalized epilepsy (GGE), and to bring new insights into the molecular pathology of GLUT1-DS that would strengthen the genotype-phenotype correlations and improve the diagnostic procedure...
November 28, 2017: Seizure: the Journal of the British Epilepsy Association
https://www.readbyqxmd.com/read/29218520/design-synthesis-and-evaluation-of-glut-inhibitors
#16
Carlotta Granchi, Tiziano Tuccinardi, Filippo Minutolo
The Warburg effect describes how most cancer cells exhibit higher-than-normal glucose consumption, not only under hypoxic conditions, but also when normal oxygen levels are present. Although glucose transporter 1 (GLUT1) has been found to play a key role in the cellular uptake of glucose, especially in cancer cells, where it is generally overexpressed, it has not been given consideration as a suitable target for the development of anticancer drugs. In this chapter, an example of molecular design and realization of novel GLUT1 inhibitors, including in silico modeling, chemical synthesis, and biological characterization, is provided...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29218517/glucose-uptake-in-heterologous-expression-systems
#17
Eunice E Lee, Richard C Wang
Understanding the physiological regulation of glucose transport requires the analysis of transporters, like GLUT1, in diverse tissue types. We document the utility of viral vectors for the stable expression of wild-type and modified GLUT1 transporter in different types of mammalian cells. Once expression of the alleles has been confirmed by Western blotting, the effect of specific mutations on the regulation of glucose transport can be measured through a previously described radiolabeled glucose transport assay...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29218514/crystallization-and-structural-determination-of-the-human-glucose-transporters-glut1-and-glut3
#18
Dong Deng, Nieng Yan
Overexpression, purification, and crystallization of eukaryotic membrane proteins represent a major challenge for structural biology. In recent years, we have solved the crystal structures of the human glucose transporters GLUT1 in the inward-open conformation at 3.17 Å resolution and GLUT3 in the outward-open and occluded conformations at 2.4 and 1.5 Å resolutions, respectively. Structural elucidation of these transporters in three distinct functional states reveal the molecular basis for the alternating access transport cycle of this prototypal solute carrier family...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29218513/expression-and-purification-of-rat-glucose-transporter-1-in-pichia-pastoris
#19
Raminta Venskutonytė, Karin Elbing, Karin Lindkvist-Petersson
Large amounts of pure and homogenous protein are a prerequisite for several biochemical and biophysical analyses, and in particular if aiming at resolving the three-dimensional protein structure. Here we describe the production of the rat glucose transporter 1 (GLUT1), a membrane protein facilitating the transport of glucose in cells. The protein is recombinantly expressed in the yeast Pichia pastoris. It is easily maintained and large-scale protein production in shaker flasks, as commonly performed in academic research laboratories, results in relatively high yields of membrane protein...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29212930/control-of-htlv-1-infection-by-eliminating-envelope-protein-positive-cells-with-recombinant-vesicular-stomatitis-viruses-encoding-htlv-1-primary-receptor
#20
Kenta Tezuka, Kazu Okuma, Madoka Kuramitsu, Sahoko Matsuoka, Reiko Tanaka, Yuetsu Tanaka, Isao Hamaguchi
Human T-cell leukemia virus type 1 (HTLV-1) infection causes adult T-cell leukemia (ATL), which is frequently resistant to current available therapies and has a very poor prognosis. To prevent the development of ATL among carriers it is important to control HTLV-1-infected cells in infected individuals. Therefore, the establishment of novel therapies with drugs specifically targeting infected cells is urgently required. This study aimed to develop a potential therapy by generating recombinant vesicular stomatitis viruses (rVSVs) that lack an envelope glycoprotein G and instead encode HTLV-1 receptor(s) with human glucose transporter 1 (GLUT1), neuropilin 1 (NRP1), or heparan sulfate proteoglycans (HSPGs) including syndecan 1 (SDC1), designated as VSVΔG-GL, VSVΔG-NP, or VSVΔG-SD, respectively...
December 6, 2017: Journal of Virology
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