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https://www.readbyqxmd.com/read/28624579/epigenome-wide-association-study-identifies-methylation-sites-associated-with-liver-enzymes-and-hepatic-steatosis
#1
Jana Nano, Mohsen Ghanbari, Wenshi Wang, Paul S de Vries, Klodian Dhana, Taulant Muka, André G Uitterlinden, Joyce B J van Meurs, Albert Hofman, Oscar H Franco, Qiuwei Pan, Sarwa Darwish Murad, Abbas Dehghan
BACKGROUND & AIMS: Epigenetic mechanisms might be involved in the regulation of liver enzyme level. We aimed to identify CpG sites at which DNA methylation levels are associated with blood levels of liver enzymes and hepatic steatosis. METHODS: We conducted an epigenome-wide association study in whole blood for liver enzymes levels including gamma-glutamyl transferase (GGT), alanine aminotransferase (ALT), and aspartate aminotransferase (AST), among a discovery set of 731 participants of the Rotterdam Study and sought replication in a non-overlapping sample of 719 individuals...
June 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28609484/the-clinical-and-prognostic-correlation-of-hrnpm-and-slc1a5-in-pathogenesis-and-prognosis-in-epithelial-ovarian-cancer
#2
Kathrine Bjersand, Tomas Seidal, Inger Sundström-Poromaa, Helena Åkerud, Ingiridur Skirnisdottir
OBJECTIVES: To evaluate the prognostic effect of the Heterogeneous nuclear ribonucleoprotein type M (HNRPM) and Solute carrier 1A5 (SLC1A5) in FIGO-stages I-II epithelial ovarian cancer. METHODS: A retrospective cohort study was designed to investigate the prognostic effect of HNRPM and SLC1A5, and the association with clinical-pathologic characteristics in 131 patients with FIGO-stages I-II epithelial ovarian cancer. Tissue microarrays were constructed and protein levels were assessed by immunohistochemistry (IHC)...
2017: PloS One
https://www.readbyqxmd.com/read/28571990/optimal-ratios-of-essential-amino-acids-stimulate-%C3%AE-casein-synthesis-via-activation-of-the-mammalian-target-of-rapamycin-signaling-pathway-in-mac-t-cells-and-bovine-mammary-tissue-explants
#3
S S Li, J J Loor, H Y Liu, L Liu, A Hosseini, W S Zhao, J X Liu
Amino acids are the building blocks of proteins and serve as key molecular components upstream of the signaling pathways that regulate protein synthesis. The objective of this study was to systematically investigate the effect of essential AA ratios on milk protein synthesis in vitro and to elucidate some of the underlying mechanisms. Triplicate cultures of MAC-T cells and bovine mammary tissue explants (MTE) were incubated with the optimal AA ratio (OPAA; Lys:Met, 2.9:1; Thr:Phe, 1.05:1; Lys:Thr, 1.8:1; Lys:His, 2...
May 29, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28553292/asct2-slc1a5-deficient-mice-have-normal-b-cell-development-proliferation-and-antibody-production
#4
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/28522974/low-dose-paclitaxel-inhibits-tumor-cell-growth-by-regulating-glutaminolysis-in-colorectal-carcinoma-cells
#5
Chaoxiang Lv, Hao Qu, Wanyun Zhu, Kaixiang Xu, Anyong Xu, Baoyu Jia, Yubo Qing, Honghui Li, Hong-Jiang Wei, Hong-Ye Zhao
Paclitaxel (PTX) is a natural alkaloid isolated from the bark of a tree, Taxus brevifolia, and is currently used to treat a variety of tumors. Recently, it has been found that low-dose PTX is a promising treatment for some cancers, presenting few side effects. However, antitumor mechanisms of low-dose PTX (<1 nM) have rarely been illuminated. Here we report a new antitumor mechanism of low-dose PTX in colorectal carcinoma cells. We treated colorectal carcinoma HCT116 cells with PTX at 0.1 and 0.3 nM for 0, 1, 2, or 3 days, and found that low-dose PTX inhibits cell growth without altering cell morphology and cell cycle...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28512249/p62-sqstm1-cooperates-with-hyperactive-mtorc1-to-regulate-glutathione-production-maintain-mitochondrial-integrity-and-promote-tumorigenesis
#6
Hilaire C Lam, Christian V Baglini, Alicia Llorente Lope, Andrey A Parkhitko, Heng-Jia Liu, Nicola Alesi, Izabela A Malinowska, Darius Ebrahimi-Fakhari, Afshin Saffari, Jane J Yu, Ana Pereira, Damir Khabibullin, Barbara Ogorek, Julie Nijmeh, Taylor Kavanagh, Adam Handen, Stephen Y Chan, John M Asara, William M Oldham, Maria T Diaz-Meco, Jorge Moscat, Mustafa Sahin, Carmen Priolo, Elizabeth P Henske
p62/sequestosome-1 (SQSTM1) is a multifunctional adaptor protein and autophagic substrate that accumulates in cells with hyperactive mTORC1, such as kidney cells with mutations in the tumor suppressor genes tuberous sclerosis complex (TSC)1 or TSC2. Here we report that p62 is a critical mediator of TSC2-driven tumorigenesis, as Tsc2(+/-) and Tsc2f/f Ksp-CreERT2(+) mice crossed to p62(-/-) mice were protected from renal tumor development. Metabolic profiling revealed that depletion of p62 in Tsc2-null cells decreased intracellular glutamine, glutamate, and glutathione (GSH)...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28507054/glutamine-transporters-are-targets-of-multiple-oncogenic-signaling-pathways-in-prostate-cancer
#7
Mark A White, Chenchu Lin, Kimal Rajapakshe, Jianrong Dong, Yan Shi, Efrosini Tsouko, Ratna Mukhopadhyay, Diana Jasso, Wajahat Dawood, Cristian Coarfa, Daniel E Frigo
Despite the known importance of androgen receptor (AR) signaling in prostate cancer (PCa), the processes downstream of AR that drive disease development and progression remain poorly understood. This knowledge gap has thus limited the ability to treat cancer. Here, it is demonstrated that androgens increase the metabolism of glutamine in PCa cells. This metabolism was required for maximal cell growth under conditions of serum starvation. Mechanistically, AR signaling promoted glutamine metabolism by increasing the expression of the glutamine transporters SLC1A4 and SLC1A5, genes commonly overexpressed in PCa...
May 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28497545/milk-protein-synthesis-is-regulated-by-t1r1-t1r3-a-g-protein-coupled-taste-receptor-through-the-mtor-pathway-in-the-mouse-mammary-gland
#8
Junqiang Liu, Yanhong Wang, Dewei Li, Yanhuan Wang, Menglu Li, Caifa Chen, Xingtang Fang, Hong Chen, Chunlei Zhang
SCOPE: Understanding the regulatory mechanism of milk protein synthesis is important to develop strategies to improve milk protein and enhance lactation performance. mTOR pathway is a crucial modulator of protein synthesis. In this study, we want to investigate if T1R1/T1R3 can regulate milk protein synthesis and mediate the mTOR pathway in the mice mammary gland in vivo. METHODS AND RESULTS: T1R1 knockout mice, WT mice, and mammary explants were used. The weigh-suckle-weigh method was used to quantify the milk yield...
May 12, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28377902/role-of-glycosylation-deglycolysation-processes-in-francisella-tularensis-pathogenesis
#9
REVIEW
Monique Barel, Alain Charbit
Francisella tularensis is able to invade, survive and replicate inside a variety of cell types. However, in vivo F. tularensis preferentially enters host macrophages where it rapidly escapes to the cytosol to avoid phagosomal stresses and to multiply to high numbers. We previously showed that human monocyte infection by F. tularensis LVS triggered deglycosylation of the glutamine transporter SLC1A5. However, this deglycosylation, specifically induced by Francisella infection, was not restricted to SLC1A5, suggesting that host protein deglycosylation processes in general might contribute to intracellular bacterial adaptation...
2017: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/28370287/a-functional-mammalian-target-of-rapamycin-complex-1-signaling-is-indispensable-for-c-myc-driven-hepatocarcinogenesis
#10
Pin Liu, Mengmeng Ge, Junjie Hu, Xiaolei Li, Li Che, Kun Sun, Lili Cheng, Yuedong Huang, Maria G Pilo, Antonio Cigliano, Giovanni M Pes, Rosa M Pascale, Stefania Brozzetti, Gianpaolo Vidili, Alberto Porcu, Antonio Cossu, Giuseppe Palmieri, Maria C Sini, Silvia Ribback, Frank Dombrowski, Junyan Tao, Diego F Calvisi, Ligong Chen, Xin Chen
Amplification and/or activation of the c-Myc proto-oncogene is one of the leading genetic events along hepatocarcinogenesis. The oncogenic potential of c-Myc has been proven experimentally by the finding that its overexpression in the mouse liver triggers tumor formation. However, the molecular mechanism whereby c-Myc exerts its oncogenic activity in the liver remains poorly understood. Here, we demonstrate that the mammalian target of rapamycin complex 1 (mTORC1) cascade is activated and necessary for c-Myc-dependent hepatocarcinogenesis...
July 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28043791/the-alteration-of-serine-transporter-activity-in-a-cell-line-model-of-amyotrophic-lateral-sclerosis-als
#11
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/27898344/may-glutamine-addiction-drive-the-delivery-of-antitumor-cisplatin-based-pt-iv-prodrugs
#12
Mauro Ravera, Elisabetta Gabano, Stefano Tinello, Ilaria Zanellato, Domenico Osella
A small series of Pt(IV) prodrugs containing Gln-like (Gln=glutamine) axial ligands has been designed with the aim to take advantage of the increased demand of Gln showed by some cancer cells (glutamine addiction). In complex 4 the Gln, linked through the α-carboxylic group is recognized by the Gln transporters, in particular by the solute carrier transporter SLC1A5. All compounds showed cellular accumulation, as well as antiproliferative activity, related to their lipophilicity, as already demonstrated for the majority of Pt(IV) prodrugs, that enter cells mainly by passive diffusion...
February 2017: Journal of Inorganic Biochemistry
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
#13
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/27677588/circrna-expression-pattern-and-circrna-mirna-mrna-network-in-the-pathogenesis-of-nonalcoholic-steatohepatitis
#14
Xi Jin, Chun-Yan Feng, Zun Xiang, Yi-Peng Chen, You-Ming Li
The pathogenesis of nonalcoholic steatohepatitis (NASH) is still unclear, where involvement of circRNA is considered for its active role as "miRNA sponge". Therefore, we aimed to investigate the circRNA expression pattern in NASH and further construct the circRNA-miRNA-mRNA network for in-depth mechanism exploration. Briefly, NASH mice model was established by Methionine and choline deficiency (MCD) diet feeding. Liver circRNA and mRNA profile was initially screened by microarray and ensuing qRT-PCR verification was carried out...
October 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27651314/nutritional-stress-induced-by-tryptophan-degrading-enzymes-results-in-atf4-dependent-reprogramming-of-the-amino-acid-transporter-profile-in-tumor-cells
#15
Elina Timosenko, Hemza Ghadbane, Jonathan D Silk, Dawn Shepherd, Uzi Gileadi, Lauren J Howson, Robert Laynes, Qi Zhao, Robert L Strausberg, Lars R Olsen, Stephen Taylor, Francesca M Buffa, Richard Boyd, Vincenzo Cerundolo
Tryptophan degradation is an immune escape strategy shared by many tumors. However, cancer cells' compensatory mechanisms remain unclear. We demonstrate here that a shortage of tryptophan caused by expression of indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) resulted in ATF4-dependent upregulation of several amino acid transporters, including SLC1A5 and its truncated isoforms, which in turn enhanced tryptophan and glutamine uptake. Importantly, SLC1A5 failed to be upregulated in resting human T cells kept under low tryptophan conditions but was enhanced upon cognate antigen T-cell receptor engagement...
November 1, 2016: Cancer Research
https://www.readbyqxmd.com/read/27585642/genome-wide-dna-methylation-patterns-in-cd4-t-cells-from-chinese-han-patients-with-rheumatoid-arthritis
#16
Shicheng Guo, Qi Zhu, Ting Jiang, Rongsheng Wang, Yi Shen, Xiao Zhu, Yan Wang, Fengmin Bai, Qin Ding, Xiaodong Zhou, Guangjie Chen, Dong Yi He
INTRODUCTION: Rheumatoid arthritis (RA) is an autoimmune disease that causes chronic inflammation of the joints. Recent evidence indicated the epigenetic changes may contribute to the pathogenesis of RA. METHOD: To understand the extent and nature of dysregulated DNA methylation in RA CD4T cells, we performed a genome-wide DNA methylation study in CD4 + T cells in 12 RA patients compared to 12 matched normal healthy controls. Cytosine methylation status was quantified with Illumina methylation 450K microarray...
May 2017: Modern Rheumatology
https://www.readbyqxmd.com/read/27539583/amino-acids-regulate-mtor-pathway-and-milk-protein-synthesis-in-a-mouse-mammary-epithelial-cell-line-is-partly-mediated-by-t1r1-t1r3
#17
YanHong Wang, JunQiang Liu, Hui Wu, XingTang Fang, Hong Chen, ChunLei Zhang
PURPOSE: The mechanism of dietary amino acids in regulating milk protein synthesis at the translational level is not well understood. Numerous studies have shown that the amino acid signal is transferred through the mammalian target of rapamycin (mTOR) pathway; however, the extracellular amino acid-sensing mechanism that activates mTOR complex 1 is unknown. We tested the hypotheses that the T1R1/T1R3 heterodimer functions as a direct sensor of the fed state and amino acid availability preceding the mTOR pathway and affects milk protein synthesis in mammary epithelial cells...
August 18, 2016: European Journal of Nutrition
https://www.readbyqxmd.com/read/27450723/asct2-slc1a5-is-an-egfr-associated-protein-that-can-be-co-targeted-by-cetuximab-to-sensitize-cancer-cells-to-ros-induced-apoptosis
#18
Haiquan Lu, Xinqun Li, Yang Lu, Songbo Qiu, Zhen Fan
Therapeutic targeting of ASCT2, a glutamine transporter that plays a major role in glutamine uptake in cancer cells, is challenging because ASCT2 also has a biological role in normal tissues. In this study, we report our novel finding that ASCT2 is physically associated in a molecular complex with epidermal growth factor receptor (EGFR), which is often overexpressed in human head and neck squamous cell carcinoma (HNSCC). Furthermore, we found that ASCT2 can be co-targeted by cetuximab, an EGFR antibody approved for treating metastatic HNSCC...
October 10, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27344174/inhibition-of-glucose-metabolism-prevents-glycosylation-of-the-glutamine-transporter-asct2-and-promotes-compensatory-lat1-upregulation-in-leukemia-cells
#19
Florence Polet, Ruben Martherus, Cyril Corbet, Adan Pinto, Olivier Feron
Leukemia cells are highly dependent on glucose and glutamine as bioenergetic and biosynthetic fuels. Inhibition of the metabolism of glucose but also of glutamine is thus proposed as a therapeutic modality to block leukemia cell growth. Since glucose also supports protein glycosylation, we wondered whether part of the growth inhibitory effects resulting from glycolysis inhibition could indirectly result from a defect in glycosylation of glutamine transporters. We found that ASCT2/SLC1A5, a major glutamine transporter, was indeed deglycosylated upon glucose deprivation and 2-deoxyglucose exposure in HL-60 and K-562 leukemia cells...
July 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/27272177/d-serine-is-a-substrate-for-neutral-amino-acid-transporters-asct1-slc1a4-and-asct2-slc1a5-and-is-transported-by-both-subtypes-in-rat-hippocampal-astrocyte-cultures
#20
Alan C Foster, Jill Farnsworth, Genevieve E Lind, Yong-Xin Li, Jia-Ying Yang, Van Dang, Mahmud Penjwini, Veena Viswanath, Ursula Staubli, Michael P Kavanaugh
N-methyl-D-aspartate (NMDA) receptors play critical roles in synaptic transmission and plasticity. Activation of NMDA receptors by synaptically released L-glutamate also requires occupancy of co-agonist binding sites in the tetrameric receptor by either glycine or D-serine. Although D-serine appears to be the predominant co-agonist at synaptic NMDA receptors, the transport mechanisms involved in D-serine homeostasis in brain are poorly understood. In this work we show that the SLC1 amino acid transporter family members SLC1A4 (ASCT1) and SLC1A5 (ASCT2) mediate homo- and hetero-exchange of D-serine with physiologically relevant kinetic parameters...
2016: PloS One
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