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SLC1A5

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https://www.readbyqxmd.com/read/29729916/short-communication-high-incubation-temperature-in-bovine-mammary-epithelial-cells-reduced-the-activity-of-the-mtor-signaling-pathway
#1
J D Kaufman, K R Kassube, R A Almeida, A G Ríus
Hyperthermia alters utilization of AA in protein synthesis and cell-signaling activity in bovine mammary cells. Essential AA and insulin regulate translation of proteins by controlling the activity of mammalian target of rapamycin (mTOR) signaling pathway. The objectives of this study were to evaluate (1) the effects of incubation temperature on the mTOR signaling pathway and transcription of AA transporters in a bovine mammary alveolar cell line (MAC-T) and (2) the combined effects of incubation temperature and insulin on the mTOR signaling pathway in this cell line...
May 2, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29671030/abnormal-islet-sphingolipid-metabolism-in-type-1-diabetes
#2
Laurits J Holm, Lars Krogvold, Jane P Hasselby, Simranjeet Kaur, Laura A Claessens, Mark A Russell, Clayton E Mathews, Kristian F Hanssen, Noel G Morgan, Bobby P C Koeleman, Bart O Roep, Ivan C Gerling, Flemming Pociot, Knut Dahl-Jørgensen, Karsten Buschard
AIMS/HYPOTHESIS: Sphingolipids play important roles in beta cell physiology, by regulating proinsulin folding and insulin secretion and in controlling apoptosis, as studied in animal models and cell cultures. Here we investigate whether sphingolipid metabolism may contribute to the pathogenesis of human type 1 diabetes and whether increasing the levels of the sphingolipid sulfatide would prevent models of diabetes in NOD mice. METHODS: We examined the amount and distribution of sulfatide in human pancreatic islets by immunohistochemistry, immunofluorescence and electron microscopy...
April 18, 2018: Diabetologia
https://www.readbyqxmd.com/read/29669285/kap1-regulates-regulatory-t-cell-function-and-proliferation-in-both-foxp3-dependent-and-independent-manners
#3
Shigeru Tanaka, Christian Pfleger, Jen-Feng Lai, Florence Roan, Shao-Cong Sun, Steven F Ziegler
Regulatory T cells (Tregs) are indispensable for the establishment of tolerance of self-antigens in animals. The transcriptional regulator Foxp3 is critical for Treg development and function, controlling the expression of genes important for Tregs through interactions with binding partners. We previously reported KAP1 as a binding partner of FOXP3 in human Tregs, but the mechanisms by which KAP1 affects Treg function were unclear. In this study, we analyzed mice with Treg-specific deletion of KAP1 and found that they develop spontaneous autoimmune disease...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29563155/sorting-nexin-27-snx27-regulates-the-trafficking-and-activity-of-the-glutamine-transporter-asct2
#4
Zhe Yang, Jordan Follett, Markus C Kerr, Thomas Clairfeuille, Mintu Chandra, Brett M Collins, Rohan D Teasdale
The Alanine, Serine, Cysteine-preferring Transporter 2 (ASCT2; SLC1A5) is responsible for the uptake of glutamine into cells, a major source of cellular energy and a key regulator of mammalian Target of Rapamycin (mTOR) activation. Furthermore, ASCT2 expression has reported in several human cancers making it a potential target for both diagnostic and therapeutic purposes. Here we identify ASCT2 as a membrane trafficked cargo molecule, sorted through a direct interaction with the PDZ domain of Sorting Nexin 27 (SNX27)...
March 21, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29542325/metformin-modifies-glutamine-metabolism-in-an-in-vitro-and-in-vivo-model-of-hepatic-encephalopathy
#5
Antonio Gil-Gomez, Ana Isabel Gómez-Sotelo, Isidora Ranchal, Ángela Rojas, Marta García-Valdecasas, Rocío Muñoz-Hernández, Rocío Gallego-Durán, Javier Ampuero, Manuel Romero Gómez
AIM: to analyze the effect of metformin on ammonia production derived from glutamine metabolism in vitro and in vivo. METHODS: twenty male Wistar rats were studied for 28 days after a porto-caval anastomosis (n = 16) or a sham operation (n = 4). Porto-caval shunted animals were randomized into two groups (n = 8) and either received 30 mg/kg/day of metformin for two weeks or were control animals. Plasma ammonia concentration, Gls gene expression and K-type glutaminase activity were measured in the small intestine, muscle and kidney...
March 15, 2018: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/29495336/cys-site-directed-mutagenesis-of-the-human-slc1a5-asct2-transporter-structure-function-relationships-and-crucial-role-of-cys467-for-redox-sensing-and-glutamine-transport
#6
Mariafrancesca Scalise, Lorena Pochini, Lara Console, Gilda Pappacoda, Piero Pingitore, Kristina Hedfalk, Cesare Indiveri
The human plasma membrane transporter ASCT2 is responsible for mediating Na- dependent antiport of neutral amino acids. New insights into structure/function relationships were unveiled by a combined approach of recombinant over-expression, site-directed mutagenesis, transport assays in proteoliposomes and bioinformatics. WT and Cys mutants of hASCT2 were produced in P. pastoris and purified for functional assay. The reactivity towards SH reducing and oxidizing agents of WT protein was investigated and opposite effects were revealed; transport activity increased upon treatment with the Cys reducing agent DTE, i...
February 25, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29455869/overexpression-of-slc1a5-in-lymph-node-metastases-outperforms-assessment-in-the-primary-as-a-negative-prognosticator-in-non-small-cell-lung-cancer
#7
Agnes Csanadi, Annika Oser, Konrad Aumann, Vera Gumpp, Justyna Rawluk, Ursula Nestle, Claudia Kayser, Sebastian Wiesemann, Martin Werner, Gian Kayser
Despite recent advances in therapeutic options, lung cancer is the leading cause of death among malignant diseases worldwide. Glutamine-dependence is an established attribute in cancer tissue with emerging importance as a diagnostic and therapeutic target. We analysed the expression of SLC1a5, a major glutamine transporter, in the primary tumour and corresponding nodal metastasis of non-small cell lung cancer (NSCLC) to investigate its biological impact. Expression of SLC1a5 was analysed by immunohistochemistry in 259 NSCLC and in 142 nodal metastases and correlated with clinicopathological parameters including overall survival...
April 2018: Pathology
https://www.readbyqxmd.com/read/29381896/effects-of-dietary-spermine-supplementation-on-cell-cycle-apoptosis-and-amino-acid-transporters-of-the-thymus-and-spleen-in-piglets
#8
Wei Cao, Xianjian Wu, Gang Jia, Hua Zhao, Xiaoling Chen, Caimei Wu, Jingyi Cai, Jing Wang, Guangmang Liu
Objective: This study investigated whether spermine supplementation could regulate cell cycle, apoptosis, and amino acid transporter-related genes expression in the thymus and spleen of early weaned piglets. Methods: Eighty female piglets were randomly distributed to receive adequate nutrients supplemented with spermine (0.4 mmol kg-1 body weight 24h-1) or to be provided with restricted nourishment supplemented with normal saline for 7 h or 3, 6, or 9 d in pairs...
January 26, 2018: Asian-Australasian Journal of Animal Sciences
https://www.readbyqxmd.com/read/29363109/inhibition-of-slc1a5-sensitizes-colorectal-cancer-to-cetuximab
#9
Huanrong Ma, Zhenzhen Wu, Jianjun Peng, Yang Li, Hongxiang Huang, Yi Liao, Minyu Zhou, Li Sun, Na Huang, Min Shi, Jianping Bin, Yulin Liao, Jinjun Rao, Lin Wang, Wangjun Liao
Cetuximab resistance is a key barrier in treating metastatic colorectal cancer (mCRC). Targeting of metabolic resources import could resensitize drug-resistant cancer cells to anticancer treatments. Here we showed that the expression of the glutamine transporter solute carrier 1 family member 5 (SLC1A5) in clinical CRC samples of patients resisted to cetuximab was significantly higher than in those of patients responded to cetuximab. Inhibition of SLC1A5 by shRNA-mediated gene silencing or pharmacological inhibitor significantly suppressed the growth of CRC...
June 15, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29348676/mir-137-regulates-ferroptosis-by-targeting-glutamine-transporter-slc1a5-in-melanoma
#10
Meiying Luo, Longfei Wu, Kexin Zhang, Hong Wang, Tian Zhang, Lucas Gutierrez, Douglas O'Connell, Peng Zhang, Yu Li, Tongtong Gao, Wenyan Ren, Yongfei Yang
Ferroptosis is a regulated form of cell death driven by small molecules or conditions that induce lipid-based reactive oxygen species (ROS) accumulation. This form of iron-dependent cell death is morphologically and genetically distinct from apoptosis, necroptosis, and autophagy. miRNAs are known to play crucial roles in diverse fundamental biological processes. However, to date no study has reported miRNA-mediated regulation of ferroptosis. Here we show that miR-137 negatively regulates ferroptosis by directly targeting glutamine transporter SLC1A5 in melanoma cells...
January 18, 2018: Cell Death and Differentiation
https://www.readbyqxmd.com/read/29337138/let-7-suppresses-b-cell-activation-through-restricting-the-availability-of-necessary-nutrients
#11
Shuai Jiang, Wei Yan, Shizhen Emily Wang, David Baltimore
The control of uptake and utilization of necessary extracellular nutrients-glucose and glutamine-is an important aspect of B cell activation. Let-7 is a family of microRNAs known to be involved in metabolic control. Here, we employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters to show that let-7adf specifically inhibits T cell-independent (TI) antigen-induced immunoglobulin (Ig)M antibody production...
February 6, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29326164/the-glutamine-transporter-asct2-slc1a5-promotes-tumor-growth-independently-of-the-amino-acid-transporter-lat1-slc7a5
#12
Yann Cormerais, Pierre André Massard, Milica Vucetic, Sandy Giuliano, Eric Tambutté, Jerome Durivault, Valérie Vial, Hitoshi Endou, Michael F Wempe, Scott K Parks, Jacques Pouyssegur
The transporters for glutamine and essential amino acids, ASCT2 (solute carrier family 1 member 5, SLC1A5) and LAT1 (solute carrier family 7 member 5, SLC7A5), respectively, are overexpressed in aggressive cancers and have been identified as cancer-promoting targets. Moreover, previous work has suggested that glutamine influx via ASCT2 triggers essential amino acids entry via the LAT1 exchanger, thus activating mechanistic target of rapamycin complex 1 (mTORC1) and stimulating growth. Here, to further investigate whether these two transporters are functionally coupled, we compared the respective knockout (KO) of either LAT1 or ASCT2 in colon (LS174T) and lung (A549) adenocarcinoma cell lines...
February 23, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29295993/structural-characterisation-reveals-insights-into-substrate-recognition-by-the-glutamine-transporter-asct2-slc1a5
#13
Amanda J Scopelliti, Josep Font, Robert J Vandenberg, Olga Boudker, Renae M Ryan
Cancer cells undergo a shift in metabolism where they become reliant on nutrients such as the amino-acid glutamine. Glutamine enters the cell via the alanine/serine/cysteine transporter 2 (ASCT2) that is upregulated in several cancers to maintain an increased supply of this nutrient and are therefore an attractive target in cancer therapeutic development. ASCT2 belongs to the glutamate transporter (SLC1A) family but is the only transporter in this family able to transport glutamine. The structural basis for glutamine selectivity of ASCT2 is unknown...
January 2, 2018: Nature Communications
https://www.readbyqxmd.com/read/29208682/the-receptor-tyrosine-kinase-epha2-promotes-glutamine-metabolism-in-tumors-by-activating-the-transcriptional-coactivators-yap-and-taz
#14
Deanna N Edwards, Verra M Ngwa, Shan Wang, Eileen Shiuan, Dana M Brantley-Sieders, Laura C Kim, Albert B Reynolds, Jin Chen
Malignant tumors reprogram cellular metabolism to support cancer cell proliferation and survival. Although most cancers depend on a high rate of aerobic glycolysis, many cancer cells also display addiction to glutamine. Glutamine transporters and glutaminase activity are critical for glutamine metabolism in tumor cells. We found that the receptor tyrosine kinase EphA2 activated the TEAD family transcriptional coactivators YAP and TAZ (YAP/TAZ), likely in a ligand-independent manner, to promote glutamine metabolism in cells and mouse models of HER2-positive breast cancer...
December 5, 2017: Science Signaling
https://www.readbyqxmd.com/read/29198723/dna-methylation-analysis-identifies-loci-for-blood-pressure-regulation
#15
Melissa A Richard, Tianxiao Huan, Symen Ligthart, Rahul Gondalia, Min A Jhun, Jennifer A Brody, Marguerite R Irvin, Riccardo Marioni, Jincheng Shen, Pei-Chien Tsai, May E Montasser, Yucheng Jia, Catriona Syme, Elias L Salfati, Eric Boerwinkle, Weihua Guan, Thomas H Mosley, Jan Bressler, Alanna C Morrison, Chunyu Liu, Michael M Mendelson, André G Uitterlinden, Joyce B van Meurs, Oscar H Franco, Guosheng Zhang, Yun Li, James D Stewart, Joshua C Bis, Bruce M Psaty, Yii-Der Ida Chen, Sharon L R Kardia, Wei Zhao, Stephen T Turner, Devin Absher, Stella Aslibekyan, John M Starr, Allan F McRae, Lifang Hou, Allan C Just, Joel D Schwartz, Pantel S Vokonas, Cristina Menni, Tim D Spector, Alan Shuldiner, Coleen M Damcott, Jerome I Rotter, Walter Palmas, Yongmei Liu, Tomáš Paus, Steve Horvath, Jeffrey R O'Connell, Xiuqing Guo, Zdenka Pausova, Themistocles L Assimes, Nona Sotoodehnia, Jennifer A Smith, Donna K Arnett, Ian J Deary, Andrea A Baccarelli, Jordana T Bell, Eric Whitsel, Abbas Dehghan, Daniel Levy, Myriam Fornage
Genome-wide association studies have identified hundreds of genetic variants associated with blood pressure (BP), but sequence variation accounts for a small fraction of the phenotypic variance. Epigenetic changes may alter the expression of genes involved in BP regulation and explain part of the missing heritability. We therefore conducted a two-stage meta-analysis of the cross-sectional associations of systolic and diastolic BP with blood-derived genome-wide DNA methylation measured on the Infinium HumanMethylation450 BeadChip in 17,010 individuals of European, African American, and Hispanic ancestry...
December 7, 2017: American Journal of Human Genetics
https://www.readbyqxmd.com/read/29164275/dna-methylation-markers-associated-with-type-2-diabetes-fasting-glucose-and-hba-1c-levels-a-systematic-review-and-replication-in-a-case-control-sample-of-the-lifelines-study
#16
Eliza Walaszczyk, Mirjam Luijten, Annemieke M W Spijkerman, Marc J Bonder, Helen L Lutgers, Harold Snieder, Bruce H R Wolffenbuttel, Jana V van Vliet-Ostaptchouk
AIMS/HYPOTHESIS: Epigenetic mechanisms may play an important role in the aetiology of type 2 diabetes. Recent epigenome-wide association studies (EWASs) identified several DNA methylation markers associated with type 2 diabetes, fasting glucose and HbA1c levels. Here we present a systematic review of these studies and attempt to replicate the CpG sites (CpGs) with the most significant associations from these EWASs in a case-control sample of the Lifelines study. METHODS: We performed a systematic literature search in PubMed and EMBASE for EWASs to test the association between DNA methylation and type 2 diabetes and/or glycaemic traits and reviewed the search results...
February 2018: Diabetologia
https://www.readbyqxmd.com/read/29100325/effects-of-targeting-slc1a5-on-inhibiting-gastric-cancer-growth-and-tumor-development-in-vitro-and-in-vivo
#17
Jian Lu, Min Chen, Zhenhua Tao, Sumeng Gao, Yang Li, Yu Cao, Chun Lu, Xiaoping Zou
Aims: To investigate the oncogenic effects of SLC1A5 on gastric cancer development in vitro and in vivo . Methods: The expression level of SLC1A5 was detected in 70 gastric cancer paraffin-embedded tissues by immunohistochemistry and also was detected in gastric cancer cell lines by qRT-PCR and western blotting analysis. The effects of knockdown SLC1A5 were analyzed on cell proliferation, cell cycle, the ability of cell migration and invasion and growth signaling pathway in vitro ...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29020998/proteomic-profiling-of-breast-cancer-metabolism-identifies-shmt2-and-asct2-as-prognostic-factors
#18
Stephan Bernhardt, Michaela Bayerlová, Martina Vetter, Astrid Wachter, Devina Mitra, Volker Hanf, Tilmann Lantzsch, Christoph Uleer, Susanne Peschel, Jutta John, Jörg Buchmann, Edith Weigert, Karl-Friedrich Bürrig, Christoph Thomssen, Ulrike Korf, Tim Beissbarth, Stefan Wiemann, Eva Johanna Kantelhardt
BACKGROUND: Breast cancer tumors are known to be highly heterogeneous and differences in their metabolic phenotypes, especially at protein level, are less well-understood. Profiling of metabolism-related proteins harbors the potential to establish new patient stratification regimes and biomarkers promoting individualized therapy. In our study, we aimed to examine the relationship between metabolism-associated protein expression profiles and clinicopathological characteristics in a large cohort of breast cancer patients...
October 11, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28885889/a-genetic-variant-of-asct2-hampers-in-vitro-rna-splicing-and-correlates-with-human-longevity
#19
Patrizia D'Aquila, Paolina Crocco, Francesco De Rango, Cesare Indiveri, Dina Bellizzi, Giuseppina Rose, Giuseppe Passarino
Given the role of amino acid regulation for physiological and pathological cell proliferation, we investigated whether the variability of solute carrier family 1, member 5 (SLC1A5, namely ASCT2), encoding for ASCT2 protein, a major glutamine transporter, is related to longevity. A total of 607 differently aged unrelated individuals, 351 very old subjects (≥85 years, range 85-106 years, mean age 93.82 ± 4.44 years) and 256 younger controls (<85 years, range 64-84 years, mean age 73.60 ± 5.70 years) were analyzed...
September 8, 2017: Rejuvenation Research
https://www.readbyqxmd.com/read/28833899/non-invasive-assessment-of-culture-media-from-goat-cloned-embryos-associated-with-subjective-morphology-by-gas-chromatography-mass-spectroscopy-based-metabolomic-analysis
#20
Yan-Li Zhang, Guo-Min Zhang, Ruo-Xin Jia, Yong-Jie Wan, Hua Yang, Ling-Wei Sun, Le Han, Feng Wang
Pre-implantation embryo metabolism demonstrates distinctive characteristics associated with the development potential of embryos. We aim to determine if metabolic differences correlate with embryo morphology. In this study, gas chromatography - mass spectroscopy (GC-MS)-based metabolomics was used to assess the culture media of goat cloned embryos collected from high-quality (HQ) and low-quality (LQ) groups based on morphology. Expression levels of amino acid transport genes were further examined by quantitative real-time PCR...
January 2018: Animal Science Journal, Nihon Chikusan Gakkaihō
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