keyword
MENU ▼
Read by QxMD icon Read
search

Glutaminase

keyword
https://www.readbyqxmd.com/read/28218035/microrna-153-regulates-glutamine-metabolism-in-glioblastoma-through-targeting-glutaminase
#1
Zhenyang Liu, Junyu Wang, Yunjun Li, Juan Fan, Lihua Chen, Ruxiang Xu
Glioblastoma is the most aggressive manifestation of malignant gliomas and considered to be among the deadliest forms of human cancers. MicroRNAs are found to tightly regulate diverse biological processes and considered to play important roles in cancer etiology. In this study, we found that microRNA-153 was significantly downregulated in glioblastoma tissues compared to matched non-tumor tissues and in glioblastoma cell lines. To investigate the potential function of microRNA-153 in glioblastoma, we transfected glioblastoma cell line U87MG as well as U373MG with synthetic microRNA-153 oligos and observed decreased cell proliferation and increased apoptosis...
February 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28208301/biomolecular-interaction-assays-identified-dual-inhibitors-of-glutaminase-and-glutamate-dehydrogenase-that-disrupt-mitochondrial-function-and-prevent-growth-of-cancer-cells
#2
Min Zhu, Jinzhang Fang, Jingjing Zhang, Zheng Zhang, Jianhui Xie, Yan Yu, Jennifer Jin Ruan, Zhao Chen, Wei Hou, Gensheng Yang, Weike Su, Benfang Helen Ruan
Glutaminase (KGA/isoenzyme GAC) is an emerging and important drug target for cancer. Traditional methods for assaying glutaminase activity are coupled with several other enzymes. Such coupled assays do not permit the direct and stringent characterization of specific glutaminase inhibitors. Ebselen was identified as a potent 9 nM KGA inhibitor in the KGA/glutamate oxidase (GO)/horse radish peroxidase (HRP) coupled assay but showed very weak activity in inhibiting the growth of glutamine-dependent cancer cells...
February 7, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28205049/construction-of-potent-recombinant-strain-through-intergeneric-protoplast-fusion-in-endophytic-fungi-for-anticancerous-enzymes-production-using-rice-straw
#3
Mervat Morsy Abbas Ahmed El-Gendy, Salha Hassan Mastour Al-Zahrani, Ahmed Mohamed Ahmed El-Bondkly
Among all fungal endophytes isolates derived from different ethno-medical plants, the hyper-yield L-asparaginase and L-glutaminase wild strains Trichoderma sp. Gen 9 and Cladosporium sp. Gen 20 using rice straw under solid-state fermentation (SSF) were selected. The selected strains were used as parents for the intergeneric protoplast fusion program to construct recombinant strain for prompt improvement production of these enzymes in one recombinant strain. Among 21 fusants obtained, the recombinant strain AYA 20-1, with 2...
February 15, 2017: Applied Biochemistry and Biotechnology
https://www.readbyqxmd.com/read/28202527/-18f-2s-4r-4-fluoroglutamine-pet-detects-glutamine-pool-size-changes-in-triple-negative-breast-cancer-in-response-to-glutaminase-inhibition
#4
Rong Zhou, Austin R Pantel, Shihong Li, Brian P Lieberman, Karl Ploessl, Hoon Choi, Eric Blankemeyer, Hsiaoju Lee, Hank Kung, Robert H Mach, David Mankoff
Glutaminolysis is a metabolic pathway adapted by many aggressive cancers, including triple-negative breast cancers (TNBC), to utilize glutamine for survival and growth. In this study, we examined the utility of [18F](2S,4R)4-fluoroglutamine ([18F]4F-Gln) PET to measure tumor cellular glutamine pool size, whose change might reveal the pharmacodynamic (PD) effect of drugs targeting this cancer-specific metabolic pathway. High glutaminase (GLS) activity in TNBC tumors resulted in low cellular glutamine pool size assayed via high-resolution 1H magnetic resonance spectroscopy (MRS)...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28196863/conformational-changes-in-the-activation-loop-of-mitochondrial-glutaminase-c-a-direct-fluorescence-read-out-that-distinguishes-the-binding-of-allosteric-inhibitors-from-activators
#5
Clint A Stalnecker, Jon W Erickson, Richard A Cerione
The first step in glutamine catabolism is catalyzed by the mitochondrial enzyme glutaminase, with a specific isoform, glutaminase C (GAC), being highly expressed in cancer cells. GAC activation requires the formation of homo-tetramers, promoted by anionic allosteric activators such as inorganic phosphate. This leads to the proper orientation of a flexible loop proximal to the dimer-dimer interface that is essential for catalysis (i.e. the activation loop). A major class of allosteric inhibitors of GAC, with the prototype being BPTES (bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide), and the related molecule CB-839, binds to the activation loop and induces the formation of an inactive tetramer (2 inhibitors bound per active tetramer)...
February 14, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28190586/increased-expression-of-glutaminase-in-osteoblasts-promotes-macrophage-recruitment-in-periapical-lesions
#6
Kuo-Liang Hou, Sze-Kwan Lin, Sang-Heng Kok, Han-Wei Wang, Eddie Hsiang-Hua Lai, Chi-Yuan Hong, Hsiang Yang, Juo-Song Wang, Li-Deh Lin, Jenny Zwei-Chieng Chang
INTRODUCTION: Recently, we have shown that tissue hypoxia stimulates the progression of periapical lesions by up-regulating glycolysis-dependent apoptosis of osteoblasts. Other facets of hypoxia-induced metabolic reprogramming in disease pathogenesis require further investigation. In this study, we examined the connection between hypoxia-augmented glutamine catabolism in osteoblasts and the development of periapical lesions. METHODS: Primary human osteoblasts were cultured under hypoxia...
February 9, 2017: Journal of Endodontics
https://www.readbyqxmd.com/read/28185053/glutaminase-expression-is-a-poor-prognostic-factor-in-node-positive-triple-negative-breast-cancer-patients-with-a-high-level-of-tumor-infiltrating-lymphocytes
#7
Joo Young Kim, Sun-Hee Heo, Seul Ki Choi, In Hye Song, In Ah Park, Young-Ae Kim, Hye Seon Park, Suk Young Park, Won Seon Bang, Gyungyub Gong, Hee Jin Lee
Glutamine metabolism is emerging as one aspect of dysregulated metabolism of tumors. Triple-negative breast cancer (TNBC) cells are glutamine dependent, whereas luminal-type cells tend to be glutamine independent. Therefore, TNBC patients might benefit from therapies targeting glutamine metabolism. To investigate the clinical significance of glutamine metabolism, we examined expression and prognostic significance of glutaminase in tumor cells and tumor-infiltrating lymphocytes (TILs) in TNBC. We retrieved 658 surgically resected TNBCs and analyzed glutaminase expression in tumor cells and TILs by immunohistochemical staining...
February 9, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28174256/a-time-for-myc-metabolism-and-therapy
#8
Chi V Dang
The MYC oncogene is frequently deregulated in human cancers, whereas the proto-oncogene is exquisitely, tightly regulated in normal cells. Deregulated MYC drives transcriptional imbalance, thereby altering metabolism and disrupting the circadian Bmal1-Clock E-box-dependent transcriptional circuitry. Sustained oncogenic MYC expression drives a constitutive growth program with mammalian target of rapamycin (mTOR) activation that renders cells dependent on nutrients, such that glucose or glutamine deprivation could trigger cell death and key enzymes such as lactate dehydrogenase A (LDHA) and glutaminase (GLS) amenable for targeting in cancers...
February 7, 2017: Cold Spring Harbor Symposia on Quantitative Biology
https://www.readbyqxmd.com/read/28174105/physapubescin-a-natural-withanolide-as-a-kidney-type-glutaminase-kga-inhibitor
#9
Li Cheng, Can-Rong Wu, Li-Han Zhu, Hua Li, Li-Xia Chen
Kidney-type glutaminase (KGA) is over expressed in many kinds of cancers that converts glutamine to glutamate for supplying energy, and has become an object for targeted cancer therapy. The structure-based virtual ligand screening identified physapubescin, a withanolide purified from Physalis pubescens L., as a possible inhibitor of KGA with low binding energy. Enzyme inhibition experiments and cell-based assays further confirmed its inhibitory effects on KGA activity, suggesting potential applications of physapubescin and its derivatives as KGA inhibitors...
January 21, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28168879/head-and-neck-squamous-cell-carcinoma-metabolism-draws-on-glutaminolysis-and-stemness-is-specifically-regulated-by-glutaminolysis-via-aldehyde-dehydrogenase
#10
Pachiyappan Kamarajan, Thekkelnaycke M Rajendiran, Jason Kinchen, Mercedes Bermúdez, Theodora Danciu, Yvonne Lorraine Kapila
Cancer cells use alternate energetic pathways, however cancer stem cell (CSC) metabolic energetic pathways are unknown. The purpose of this study was to define the metabolic characteristics of head and neck cancer at different points of its pathogenesis with a focus on its CSC compartment. UPLC-MS/MS-profiling and GC-MS-validation studies of human head and neck cancer tissue, saliva, and plasma, were used in conjunction with in vitro and in vivo models to carry out this investigation. We identified metabolite biomarker panels that distinguish head and neck cancer from healthy controls, and confirmed involvement of glutamate and glutaminolysis...
February 7, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28149015/role-of-bioflavonoid-quercetin-on-expression-of-urea-cycle-enzymes-astrocytic-and-inflammatory-markers-in-hyperammonemic-rats
#11
Sivamani Kanimozhi, Perumal Subramanian, Sakkaravarthy Shanmugapriya, Subramanian Sathishkumar
This study evaluates the role of quercetin on the expression of urea cycle enzymes, astrocytic, neuronal and inflammatory markers in hyperammonemic rats. Hyperammonemia (provoked by intraperitonial injections of (ammonium chloride-100 mg/kg b.w for 56 days), showed diminished expression of urea cycle enzymes [carbamyl phosphate synthetase-1 (CPS-1), ornithine transcarbamylase (OTC), argininosuccinate synthetase (ASS) and arginase (ARG)] in liver and decreased expression of neuronal and astrocytic markers-glutamine synthase (GS) and phosphate activated glutaminase (PAG) in brain and increased expression of brain inflammatory markers such as interleukin 6 (IL6), inducible nitric oxide synthase (iNOS) and nuclear transcription factor kappa B (NF-κB) (by western blot analysis) and exhibited downregulated expression of soluble guanylate cyclase (sGC), glial fibrillary acidic protein (GFAP) in brain and ASS in liver investigated (by RT-PCR)...
March 2017: Indian Journal of Clinical Biochemistry: IJCB
https://www.readbyqxmd.com/read/28139703/the-differential-ability-of-asparagine-and-glutamine-in-promoting-the-closed-active-enzyme-conformation-rationalizes-the-wolinella-succinogenes-l-asparaginase-substrate-specificity
#12
Hien Anh Nguyen, Donald L Durden, Arnon Lavie
Many side effects of current FDA-approved L-asparaginases have been related to their secondary L-glutaminase activity. The Wolinella succinogenes L-asparaginase (WoA) has been reported to be L-glutaminase free, suggesting it would have fewer side effects. Unexpectedly, the WoA variant with a proline at position 121 (WoA-P121) was found to have L-glutaminase activity in contrast to Uniprot entry P50286 (WoA-S121) that has a serine residue at this position. Towards understanding how this residue impacts the L-glutaminase property, kinetic analysis was coupled with crystal structure determination of these WoA variants...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28130963/corrigendum-to-glutaminase-2-stabilizes-dicer-to-repress-snail-and-metastasis-in-hepatocellular-carcinoma-cells-383-2016-282-294
#13
Tsang-Chih Kuo, Chi-Kuan Chen, Kuo-Tai Hua, Pei Yu, Wei-Jiunn Lee, Min-Wei Chen, Yung-Ming Jeng, Ming-Hsien Chien, Kuang-Tai Kuo, Michael Hsiao, Min-Liang Kuo
No abstract text is available yet for this article.
January 25, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28122247/arginine-deprivation-inhibits-the-warburg-effect-and-upregulates-glutamine-anaplerosis-and-serine-biosynthesis-in-ass1-deficient-cancers
#14
Jeff Charles Kremer, Bethany Cheree Prudner, Sara Elaine Stubbs Lange, Gregory Richard Bean, Matthew Bailey Schultze, Caitlyn Brook Brashears, Megan DeAnna Radyk, Nathan Redlich, Shin-Cheng Tzeng, Kenjiro Kami, Laura Shelton, Aixiao Li, Zack Morgan, John Stephen Bomalaski, Takashi Tsukamoto, Jon McConathy, Loren Scott Michel, Jason Matthew Held, Brian Andrew Van Tine
Targeting defects in metabolism is an underutilized strategy for the treatment of cancer. Arginine auxotrophy resulting from the silencing of argininosuccinate synthetase 1 (ASS1) is a common metabolic alteration reported in a broad range of aggressive cancers. To assess the metabolic effects that arise from acute and chronic arginine starvation in ASS1-deficient cell lines, we performed metabolite profiling. We found that pharmacologically induced arginine depletion causes increased serine biosynthesis, glutamine anaplerosis, oxidative phosphorylation, and decreased aerobic glycolysis, effectively inhibiting the Warburg effect...
January 24, 2017: Cell Reports
https://www.readbyqxmd.com/read/28111979/a-tale-of-two-glutaminases-homologous-enzymes-with-distinct-roles-in-tumorigenesis
#15
William P Katt, Michael J Lukey, Richard A Cerione
Many cancer cells exhibit an altered metabolic phenotype, in which glutamine consumption is upregulated relative to healthy cells. This metabolic reprogramming often depends upon mitochondrial glutaminase activity, which converts glutamine to glutamate, a key precursor for biosynthetic and bioenergetic processes. Two isozymes of glutaminase exist, a kidney-type (GLS) and a liver-type enzyme (GLS2 or LGA). While a majority of studies have focused on GLS, here we summarize key findings on both glutaminases, describing their structure and function, their roles in cancer and pharmacological approaches to inhibiting their activities...
January 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28109982/altered-glutamate-metabolism-contributes-to-antiepileptogenic-effects-in-the-progression-from-focal-seizure-to-generalized-seizure-by-low-frequency-stimulation-in-the-ventral-hippocampus
#16
Hong-Liu Sun, Wei Zhu, Yu-Rong Zhang, Xiao-Hong Pan, Jun-Ru Zhang, Xiang-Ming Chen, Yu-Xia Liu, Shu-Cui Li, Qiao-Yun Wang, Da-Ping Deng
As a promising method for treating intractable epilepsy, the inhibitory effect of low-frequency stimulation (LFS) is well known, although its mechanisms remain unclear. Excessive levels of cerebral glutamate are considered a crucial factor for epilepsy. Therefore, we designed experiments to investigate the crucial parts of the glutamate cycle. We evaluated glutamine synthetase (GS, metabolizes glutamate), glutaminase (synthesizes glutamate), and glutamic acid decarboxylase (GAD, a γ-aminobutyric acid [GABA] synthetase) in different regions of the brain, including the dentate gyrus (DG), CA3, and CA1 subregions of the hippocampus, and the cortex, using western blots, immunohistochemistry, and enzyme activity assays...
January 18, 2017: Epilepsy & Behavior: E&B
https://www.readbyqxmd.com/read/28101462/identification-and-molecular-characterization-of-genes-coding-pharmaceutically-important-enzymes-from-halo-thermo-tolerant-bacillus
#17
Azam Safary, Rezvan Moniri, Maryam Hamzeh-Mivehroud, Siavoush Dastmalchi
Purpose: Robust pharmaceutical and industrial enzymes from extremophile microorganisms are main source of enzymes with tremendous stability under harsh conditions which make them potential tools for commercial and biotechnological applications. Methods: The genome of a Gram-positive halo-thermotolerant Bacillus sp. SL1, new isolate from Saline Lake, was investigated for the presence of genes coding for potentially pharmaceutical enzymes. We determined gene sequences for the enzymes laccase (CotA), l-asparaginase (ansA3, ansA1), glutamate-specific endopeptidase (blaSE), l-arabinose isomerase (araA2), endo-1,4-β mannosidase (gmuG), glutaminase (glsA), pectate lyase (pelA), cellulase (bglC1), aldehyde dehydrogenase (ycbD) and allantoinases (pucH) in the genome of Bacillus sp...
December 2016: Advanced Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28099841/targeted-inhibition-of-egfr-and-glutaminase-induces-metabolic-crisis-in-egfr-mutant-lung-cancer
#18
Milica Momcilovic, Sean T Bailey, Jason T Lee, Michael C Fishbein, Clara Magyar, Daniel Braas, Thomas Graeber, Nicholas J Jackson, Johannes Czernin, Ethan Emberley, Matthew Gross, Julie Janes, Andy Mackinnon, Alison Pan, Mirna Rodriguez, Melissa Works, Winter Zhang, Francesco Parlati, Susan Demo, Edward Garon, Kostyantyn Krysan, Tonya C Walser, Steven M Dubinett, Saman Sadeghi, Heather R Christofk, David B Shackelford
Cancer cells exhibit increased use of nutrients, including glucose and glutamine, to support the bioenergetic and biosynthetic demands of proliferation. We tested the small-molecule inhibitor of glutaminase CB-839 in combination with erlotinib on epidermal growth factor receptor (EGFR) mutant non-small cell lung cancer (NSCLC) as a therapeutic strategy to simultaneously impair cancer glucose and glutamine utilization and thereby suppress tumor growth. Here, we show that CB-839 cooperates with erlotinib to drive energetic stress and activate the AMP-activated protein kinase (AMPK) pathway in EGFR (del19) lung tumors...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28089435/jejunal-gluconeogenesis-associated-with-insulin-resistance-level-and-its-evolution-after-roux-en-y-gastric-bypass
#19
Carolina Gutierrez-Repiso, Sara Garcia-Serrano, Francisco J Moreno-Ruiz, Guillermo Alcain-Martinez, Francisca Rodriguez-Pacheco, Eduardo Garcia-Fuentes
BACKGROUND: Intestinal gluconeogenesis (GNG) may play an important role in glucose homeostasis, but there is little information about the condition in humans. OBJECTIVES: To study the relationship between intestinal GNG and insulin resistance, its association with the evolution of morbidly obese patients after bariatric surgery, and the effect of insulin and or leptin. SETTING: Regional university hospital, Malaga (Spain). METHODS: Jejunal mRNA expression of genes involved in GNG was analyzed in 3 groups of morbidly obese patients who underwent Roux-en-Y gastric bypass: with low insulin resistance (MO-low-IR), with high insulin resistance (MO-high-IR), and with type 2 diabetes treated with metformin (MO-metf-T2D)...
December 2, 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
https://www.readbyqxmd.com/read/28053289/glutaminolysis-gets-the-spotlight-in-cancer
#20
EDITORIAL
Daniel Herranz
News on: Inhibiting glutaminase in acute myeloid leukemia: Metabolic dependency of selected AML subtypes by Polina Matre et al. Oncotarget. 2016; 7(48): 79722-79735. doi: 10.18632/oncotarget.12944.
December 30, 2016: Oncotarget
keyword
keyword
103064
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"