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ASCT2

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https://www.readbyqxmd.com/read/28729677/engineering-tumour-cell-binding-synthetic-polymers-with-sensing-dense-transporters-associated-with-aberrant-glutamine-metabolism
#1
Naoki Yamada, Yuto Honda, Hiroyasu Takemoto, Takahiro Nomoto, Makoto Matsui, Keishiro Tomoda, Masamitsu Konno, Hideshi Ishii, Masaki Mori, Nobuhiro Nishiyama
Increased glutamine uptake toward the elevated glutaminolysis is one of the hallmarks of tumour cells. This aberrant glutamine metabolism has recently attracted considerable attention as a diagnostic and therapeutic target. Herein, we developed glutamine-functionalized polymer to achieve a selective high affinity to tumour cells overexpressing glutaminolysis-related transporter ASCT2. In in vitro study, our developed polymer exhibited faster and higher cellular uptake in tumour cells than that in normal cells...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28692032/epigenetic-silencing-of-microrna-137-enhances-asct2-expression-and-tumor-glutamine-metabolism
#2
J Dong, D Xiao, Z Zhao, P Ren, C Li, Y Hu, J Shi, H Su, L Wang, H Liu, B Li, P Gao, G Qing
Tumor cells must activate specific transporters to meet their increased glutamine metabolic demands. Relative to other glutamine transporters, the ASC family transporter 2 (ASCT2, also called SLC1A5) is profoundly elevated in a wide spectrum of human cancers to coordinate metabolic reprogramming and malignant transformation. Understanding the molecular mechanisms whereby tumor cells frequently upregulate this transporter is therefore vital to develop potential strategies for transporter-targeted therapies. Combining in-silico algorithms with systemic experimental screening, we herein identify the tumor suppressor microRNA, miR-137, as an essential regulator that targets ASCT2 and cancer cell glutamine metabolism...
July 10, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28625135/studying-interactions-of-drugs-with-cell-membrane-nutrient-transporters-new-frontiers-of-proteoliposome-nanotechnology
#3
Mariafrancesca Scalise, Michele Galluccio, Lorena Pochini, Lara Console, Maria Barile, Nicola Giangregorio, Annamaria Tonazzi, Cesare Indiveri
Transport systems are hydrophobic proteins localized in cell membranes where they mediate transmembrane flow of nutrients, ions and any other compounds essential for cell metabolism. More than 400 transporters of the SoLuteCarrier (SLC) group are present in human cells. Transporters take contacts also with xenobiotics, thus mediating absorption and/or interaction with these exogenous compounds. Since drugs belong to xenobiotics, transporters gained interest also in drug discovery. Transporters differentially expressed in pathological conditions are exploited as drug targets...
June 15, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28623466/increases-in-circulating-amino-acids-with-in-feed-antibiotics-correlated-with-gene-expression-of-intestinal-amino-acid-transporters-in-piglets
#4
Miao Yu, Chunlong Mu, Yuxiang Yang, Chuanjian Zhang, Yong Su, Zan Huang, Kaifan Yu, Weiyun Zhu
In-feed antibiotics have been commonly used to promote the growth performance of piglets. The antibiotics can increase protein utilization, but the underlying mechanism is largely unknown. The present study investigated the effects of in-feed antibiotics on intestinal AA transporters and receptors to test the hypothesis that the alteration of circulating AA profiles may be concomitant with the change of intestinal AA transporters and receptors. Sixteen litters of piglets at day 7 started to receive creep feed with (Antibiotic) or without (Control) antibiotic...
June 16, 2017: Amino Acids
https://www.readbyqxmd.com/read/28553292/asct2-slc1a5-deficient-mice-have-normal-b-cell-development-proliferation-and-antibody-production
#5
Etienne Masle-Farquhar, Angelika Bröer, Mehmet Yabas, Anselm Enders, Stefan Bröer
SLC1A5 (solute carrier family 1, member 5) is a small neutral amino acid exchanger that is upregulated in rapidly proliferating lymphocytes but also in many primary human cancers. Furthermore, cancer cell lines have been shown to require SLC1A5 for their survival in vitro. One of SLC1A5's primary substrates is the immunomodulatory amino acid glutamine, which plays an important role in multiple key processes, such as energy supply, macromolecular synthesis, nucleotide biosynthesis, redox homeostasis, and resistance against oxidative stress...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28536503/epigenetic-activation-of-asct2-in-the-hippocampus-contributes-to-depression-like-behavior-by-regulating-d-serine-in-mice
#6
Jiesi Wang, Ke Zhang, Xiaojuan Chen, Xiaoqian Liu, Huajing Teng, Mei Zhao, Zhongsheng Sun
The roles of D-serine in depression are raised concerned recently as an intrinsic co-agonist for the NMDA receptor. However, the mechanisms underlying its regulation are not fully elucidated. ASCT2 is a Na(+)-dependent D-serine transporter. We found that decreased D-serine and increased hippocampal ASCT2 levels correlated with chronic social defeat stress (CSDS) in mice. Lentivirus-mediated shRNA-mediated knockdown of ASCT2 and the administration of exogenous D-serine in the hippocampus alleviated CSDS-induced social avoidance and immobility...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28516268/gpna-inhibits-the-sodium-independent-transport-system-l-for-neutral-amino-acids
#7
Martina Chiu, Cosimo Sabino, Giuseppe Taurino, Massimiliano G Bianchi, Roberta Andreoli, Nicola Giuliani, Ovidio Bussolati
L-γ-Glutamyl-p-nitroanilide (GPNA) is widely used to inhibit the glutamine transporter ASCT2, although it is known that it also inhibits other sodium-dependent amino acid transporters. In a panel of human cancer cell lines, which express the system L transporters LAT1 and LAT2, GPNA inhibits the sodium-independent influx of leucine and glutamine. The kinetics of the effect suggests that GPNA is a low affinity, competitive inhibitor of system L transporters. In Hs683 human oligodendroglioma cells, the incubation in the presence of GPNA, but not ASCT2 silencing, lowers the cell content of leucine...
May 17, 2017: Amino Acids
https://www.readbyqxmd.com/read/28440528/-effect-of-asct2-gene-knock-down-by-shrna-on-biological-behaviors-of-colorectal-cancer-cells
#8
Canfeng Cai, Bing Zeng, Jun Zeng, Haiyang Xin, Chaoming Tang
OBJECTIVE: To investigate the effect of ASCT2 gene (glutamine transporter) knock-down by shRNA on biological behaviors of colorectal cancer cells. METHODS: shRNA was transfected into colorectal cancer cells Lovo and SW480 to knockdown ASCT2 mediated by Lipofectamine 2000. Reverse transcription-PCR and Western blot were used to examine the mRNA and protein expression of ASCT2. MTT and transwell assay were used to determine the proliferation and invasiveness of Lovo and SW480 cells...
April 25, 2017: Zhonghua Wei Chang Wai Ke za Zhi, Chinese Journal of Gastrointestinal Surgery
https://www.readbyqxmd.com/read/28252650/amino-acid-transporters-in-t-cell-activation-and-differentiation
#9
REVIEW
W Ren, G Liu, J Yin, B Tan, G Wu, F W Bazer, Y Peng, Y Yin
T-cell-mediated immune responses aim to protect mammals against cancers and infections, and are also involved in the pathogenesis of various inflammatory or autoimmune diseases. Cellular uptake and the utilization of nutrients is closely related to the T-cell fate decision and function. Research in this area has yielded surprising findings in the importance of amino-acid transporters for T-cell development, homeostasis, activation, differentiation and memory. In this review, we present current information on amino-acid transporters, such as LAT1 (l-leucine transporter), ASCT2 (l-glutamine transporter) and GAT-1 (γ-aminobutyric acid transporter-1), which are critically important for mediating peripheral naive T-cell homeostasis, activation and differentiation, especially for Th1 and Th17 cells, and even memory T cells...
March 2, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28174119/potential-transfer-of-neurotoxic-amino-acid-%C3%AE-n-methylamino-alanine-bmaa-from-mother-to-infant-during-breast-feeding-predictions-from-human-cell-lines
#10
Marie Andersson, Lisa Ersson, Ingvar Brandt, Ulrika Bergström
β-N-methylamino-alanine (BMAA) is a non-protein amino acid produced by cyanobacteria, diatoms and dinoflagellates. BMAA has potential to biomagnify in a terrestrial food chain, and to bioaccumulate in fish and shellfish. We have reported that administration of [(14)C]l-BMAA to lactating mice and rats results in a mother to off-spring transfer via the milk. A preferential enantiomer-specific uptake of [(14)C]l-BMAA has also been demonstrated in differentiated murine mammary epithelium HC11 cells. These findings, together with neurotoxic effects of BMAA demonstrated both in vitro and in vivo, highlight the need to determine whether such transfer could also occur in humans...
April 1, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/28112360/low-uptake-of-fluorodeoxyglucose-in-positron-emission-tomography-computed-tomography-in-ovarian-clear-cell-carcinoma-may-reflect-glutaminolysis-of-its-cancer-stem-cell-like-properties
#11
Masakazu Sato, Kei Kawana, Katsuyuki Adachi, Asaha Fujimoto, Ayumi Taguchi, Tomona Fujikawa, Mitsuyo Yoshida, Hiroe Nakamura, Haruka Nishida, Tomoko Inoue, Juri Ogishima, Satoko Eguchi, Aki Yamashita, Kensuke Tomio, Takahide Arimoto, Osamu Wada-Hiraike, Katsutoshi Oda, Takeshi Nagamatsu, Yutaka Osuga, Tomoyuki Fujii
The characteristics of ovarian cancers that showed low activation of glycolysis were investigated. Using medical records of patients with ovarian cancers who had undergone fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) prior to their primary surgery at the University of Tokyo Hospital between 2010 and 2015, we identified cases with a low uptake of FDG in PET/CT. We considered the maximum standardized uptake value (SUVmax) as the degree of glucose uptake. We investigated the properties which may account for the low activation of glycolysis in vitro...
March 2017: Oncology Reports
https://www.readbyqxmd.com/read/28057420/structure-activity-relationships-of-benzylproline-derived-inhibitors-of-the-glutamine-transporter-asct2
#12
Kurnvir Singh, Rose Tanui, Armanda Gameiro, Gilad Eisenberg, Claire Colas, Avner Schlessinger, Christof Grewer
The glutamine transporter ASCT2 has been identified as a promising target to inhibit rapid growth of cancer cells. However, ASCT2 pharmacology is not well established. In this report, we performed a systematic structure activity analysis of a series of substituted benzylproline derivatives. Substitutions on the phenyl ring resulted in compounds with characteristics of ASCT2 inhibitors. Apparent binding affinity increased with increasing hydrophobicity of the side chain. In contrast, interaction of the ASCT2 binding site with specific positions on the phenyl ring was not observed...
February 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28043791/the-alteration-of-serine-transporter-activity-in-a-cell-line-model-of-amyotrophic-lateral-sclerosis-als
#13
Na-Young Lee, Yunha Kim, Hoon Ryu, Young-Sook Kang
The alteration of d-serine levels is associated with the pathogenesis of sporadic ALS and mutant SOD1 (G93A) animal model of ALS. However, the exact mechanism of d-serine transport is not known in ALS. To better understand the distribution of d-serine in ALS, we determined the activity and the expression of serine transporter in a motor neuronal cell line model of ALS (NSC-34/hSOD1(G93A) cells). The uptake of [(3)H]d-serine was significantly lower in NSC-34/hSOD1(G93A) cells than in control NSC-34 and NSC-34/hSOD1(wt) cells...
January 29, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27885632/glutamine-metabolism-in-gliomas
#14
Monika Szeliga, Jan Albrecht
By histological, morphological criteria, and malignancy, brain tumors are classified by WHO into grades I (most benign) to IV (highly malignant), and gliomas are the most frequently occurring class throughout the grades. Similar to peripheral tumors, the growth of glia-derived tumor cells largely depends on glutamine (Gln), which is vividly taken up by the cells, using mostly ASCT2 and SN1 as Gln carriers. Tumor growth-promoting effects of Gln are associated with its phosphate-activated glutaminase (GA) (specifically KGA)-mediated degradation to glutamate (Glu) and/or with its entry to the energy- and intermediate metabolite-generating pathways related to the tricarboxylic acid cycle...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27885631/the-glutamine-transporters-and-their-role-in-the-glutamate-gaba-glutamine-cycle
#15
Renata Leke, Arne Schousboe
Glutamine is a key amino acid in the CNS, playing an important role in the glutamate/GABA-glutamine cycle (GGC). In the GGC, glutamine is transferred from astrocytes to neurons, where it will replenish the inhibitory and excitatory neurotransmitter pools. Different transporters participate in this neural communication, i.e., the transporters responsible for glutamine efflux from astrocytes and influx into the neurons, such as the members of the SNAT, LAT, y(+)LAT, and ASC families of transporters. The SNAT family consists of the transporter isoforms SNAT3 and SNAT5 that are related to efflux from the astrocytic compartment, and SNAT1 and SNAT2 that are associated with glutamine uptake into the neuronal compartment...
2016: Advances in Neurobiology
https://www.readbyqxmd.com/read/27865832/establishment-of-monoclonal-antibodies-against-cell-surface-domains-of-asct2-slc1a5-and-their-inhibition-of-glutamine-dependent-tumor-cell-growth
#16
Masayo Suzuki, Hiroe Toki, Akiko Furuya, Hiroshi Ando
Human alanine-serine-cysteine transporter 2 (ASCT2; SLC1A5) is a major transporter of the amino acid glutamine that is known to be overexpressed in certain malignant tumors. In this study, we generated specific monoclonal antibodies (MAbs) against ASCT2 by establishing an ASCT2-expressing Chinese hamster ovary cell line that was used to immunize mice and rats. The MAbs KM4008, KM4012, and KM4018 against ASCT2 were isolated through a cell-based screen; these specifically bound to ASCT2-positive cells, as determined by flow cytometry and immunoprecipitation...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27801863/nutrient-transporter-expression-in-the-jejunum-in-relation-to-body-mass-index-in-patients-undergoing-bariatric-surgery
#17
Brian A Irving, G Craig Wood, Peter N Bennotti, Ellappan Babu, Abhishek Deshpande, Michelle R Lent, Anthony Petrick, Jon Gabrielsen, William Strodel, Glenn S Gerhard, Christopher D Still, Vadivel Ganapathy, David D K Rolston
Nutrient tranters (NT) facilitate nutrient absorption and contribute to the regulation of circulating nutrients. In this cross-sectional study, we determined the associations between the level of obesity; mRNA abundance for NTs; and serum concentrations of amino acids, short-chain fatty acids, and glucose in patients with morbid obesity undergoing a Roux-en-Y gastric bypass. Proximal jejunal samples were obtained at the time of surgery from 42 patients (90% female, age = 42.6 ± 11.9 years, pre-operative body mass index (BMI) = 55...
October 29, 2016: Nutrients
https://www.readbyqxmd.com/read/27770401/non-invasive-glutamine-pet-reflects-pharmacological-inhibition-of-braf-v600e-in-vivo
#18
Michael L Schulte, Matthew R Hight, Gregory D Ayers, Qi Liu, Yu Shyr, M Kay Washington, H Charles Manning
PURPOSE: This study aimed to study whether cancer cells possess distinguishing metabolic features compared with surrounding normal cells, such as increased glutamine uptake. Given this, quantitative measures of glutamine uptake may reflect critical processes in oncology. Approximately, 10 % of patients with colorectal cancer (CRC) express BRAF (V600E) , which may be actionable with selective BRAF inhibitors or in combination with inhibitors of complementary signaling axes. Non-invasive and quantitative predictive measures of response to these targeted therapies remain poorly developed in this setting...
October 21, 2016: Molecular Imaging and Biology: MIB: the Official Publication of the Academy of Molecular Imaging
https://www.readbyqxmd.com/read/27753190/gastrointestinal-methionine-shuttle-priority-handling-of-precious-goods
#19
Lucia Mastrototaro, Gerhard Sponder, Behnam Saremi, Jörg R Aschenbach
Methionine (Met) is a neutral, sulfur-containing, essential amino acid with biological functions in the initiation and prolongation step of protein synthesis, transmethylation reactions, the synthesis of cysteine and cystine, and as a component of antioxidant systems. Its key importance is reflected by the fact that it is usually absorbed from the diet with highest efficiency among all proteinogenic amino acids but may yet not optimally support metabolism and health. As such, crystalline Met supplements are partly used in man and heavily used in production of animal species (poultry, fish, shrimps, pigs and cattle) to provide improved health and performance...
October 17, 2016: IUBMB Life
https://www.readbyqxmd.com/read/27672436/slc-transporters-structure-function-and-drug-discovery
#20
Claire Colas, Peter Man-Un Ung, Avner Schlessinger
The human Solute Carrier (SLC) transporters are important targets for drug development. Structure-based drug discovery for SLC transporters requires the description of their structure, dynamics, and mechanism of interaction with small molecule ligands and ions. The recent determination of atomic structures of human SLC transporters and their homologs, combined with improved computational power and prediction methods have led to an increased applicability of structure-based drug design methods for human SLC members...
June 1, 2016: MedChemComm
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