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Glutaminase

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https://www.readbyqxmd.com/read/28928849/glutaminase-sustains-cell-survival-via-the-regulation-of-glycolysis-and-glutaminolysis-in-colorectal-cancer
#1
Zhou Song, Bo Wei, Canrong Lu, Peiyu Li, Lin Chen
Cancer cells remodel their metabolic programs towards aerobic glycolysis and elevated glutaminolysis to meet the requirement s of rapid proliferation. Understanding how cells sense and adapt to these changes may provide new targets for therapeutic intervention. Deamination of glutamine to glutamate by glutaminase (GLS1) is an essential step in glutaminolysis. The present study revealed that the loss of GLS1 expression by RNA interference or inhibitor decreased the proliferation and viability of colorectal cancer (CRC) cells...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928633/glutaminase-and-mmp-9-downregulation-in-cortex-and-hippocampus-of-lpa1-receptor-null-mice-correlate-with-altered-dendritic-spine-plasticity
#2
Ana Peñalver, José A Campos-Sandoval, Eduardo Blanco, Carolina Cardona, Laura Castilla, Mercedes Martín-Rufián, Guillermo Estivill-Torrús, Raquel Sánchez-Varo, Francisco J Alonso, Mercedes Pérez-Hernández, María I Colado, Antonia Gutiérrez, Fernando Rodríguez de Fonseca, Javier Márquez
Lysophosphatidic acid (LPA) is an extracellular lipid mediator that regulates nervous system development and functions acting through G protein-coupled receptors (GPCRs). Here we explore the crosstalk between LPA1 receptor and glutamatergic transmission by examining expression of glutaminase (GA) isoforms in different brain areas isolated from wild-type (WT) and KOLPA1 mice. Silencing of LPA1 receptor induced a severe down-regulation of Gls-encoded long glutaminase protein variant (KGA) (glutaminase gene encoding the kidney-type isoforms, GLS) protein expression in several brain regions, particularly in brain cortex and hippocampus...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28916328/primary-hippocampal-neuronal-cell-death-induction-after-acute-and-repeated-paraquat-exposures-mediated-by-ache-variants-alteration-and-cholinergic-and-glutamatergic-transmission-disruption
#3
Javier Del Pino, Paula Moyano, Gloria Gómez Díaz, María José Anadon, Maria Jesus Diaz, José Manuel García, Margarita Lobo, Adela Pelayo, Emma Sola, María Teresa Frejo
Paraquat (PQ) is a widely used non-selective contact herbicide shown to produce memory and learning deficits after acute and repeated exposure similar to those induced in Alzheimer's disease (AD). However, the complete mechanisms through which it induces these effects are unknown. On the other hand, cholinergic and glutamatergic systems, mainly in the hippocampus, are involved on learning, memory and cell viability regulation. An alteration of hippocampal cholinergic or glutamatergic transmissions or neuronal cell loss may induce these effects...
September 12, 2017: Toxicology
https://www.readbyqxmd.com/read/28899090/synthesis-and-sensory-characteristics-of-kokumi-%C3%AE-glu-n-phe-in-the-presence-of-glutamine-and-phenylalanine-glutaminase-from-bacillus-amyloliquefaciens-or-aspergillus-oryzae-as-the-catalyst
#4
Juan Yang, Dongxiao Sun-Waterhouse, Chun Cui, Keming Dong, Wei Wang
The transpeptidase activity of glutaminase from Bacillus amyloliquefaciens (GBA) and Aspergillus oryzae (GAO) to yield γ-[Glu]n-Phe peptides were verified for the first time. In the presence of Gln and Phe, γ-Glu-Phe and γ-Glu-γ-Glu-Phe were synthesized by GAO, and γ-Glu-Phe, γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-Phe, γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe and γ-Glu-γ-Glu-γ-Glu-γ-Glu-γ-Glu-Phe were synthesized by GBA. The Km values for the transpeptidation catalysed by GBA and GAO were 47.88 and 153.92 mM (Phe as the acceptor), 84...
September 13, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28871132/an-lc-ms-approach-to-quantitative-measurement-of-ammonia-isotopologues
#5
Jessica B Spinelli, Liam P Kelley, Marcia C Haigis
Ammonia is a fundamental aspect of metabolism spanning all of phylogeny. Metabolomics, including metabolic tracing studies, are an integral part of elucidating the role of ammonia in these systems. However, current methods for measurement of ammonia are spectrophotometric, and cannot distinguish isotopologues of ammonia, significantly limiting metabolic tracing studies. Here, we describe a novel LC-MS-based method that quantitatively assesses both (14)N-and (15)N-isotopologues of ammonia in polar metabolite extracts...
September 4, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28861894/sex-differences-in-the-glutamate-signaling-pathway-in-juvenile-rats
#6
Etidal Al-Suwailem, Saba Abdi, Afaf El-Ansary
Females have been found to be at lower risk for the development of neurodevelopmental disorders than males. The greater neuroprotection in females is mostly due to female sex hormones. Estrogen is hypothesized to provide neuroprotection by suppressing the neuro-excitotoxicity induced by glutamate (Glu). This study was conducted to understand the effect of sex in modulating Glu signaling in juvenile rats. Brain tissue homogenate of 15 Wistar albino rats (9 males, 6 females) weighing 60 to 80 g and aged approximately 28 days was used...
September 1, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28844802/recent-developments-in-small-molecule-therapies-for-renal-cell-carcinoma
#7
REVIEW
Minsoo Song
Renal cell carcinoma (RCC) is the most common type of kidney cancer in adults and is known to be the 10th most common type of cancer in the world. Most of the currently available RCC drugs are tyrosine kinase inhibitors (TKIs). However, combination therapies of TKIs and immune checkpoint inhibitors such as programmed cell death protein 1 (PD-1) and programmed cell death protein 1 ligand 1 (PD-L1) inhibitors are the focus of most of the final stage clinical trials. Meanwhile, other small molecule therapies for RCC that target indoleamine-2,3-dioxygenase (IDO1), glutaminase, C-X-C chemokine receptor 4 (CXCR4), and transglutaminase 2 (TG2) are emerging as the next generation of therapeutics...
August 9, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28844150/evidence-for-altered-glutamine-metabolism-in-hiv-1-infected-primary-human-cd4-t-cells
#8
Andrea Hegedus, Maia Kavanagh Williamson, Mariam Bibi Khan, Juliana Dias Zeidler, Andrea Da Poian, Tatiana El Bacha, Eduard Struys, Hendrik Huthoff
Glutamine is a conditionally essential amino acid that is an important metabolic resource for proliferating tissues by acting as a proteinogenic amino acid, a nitrogen donor for biosynthetic reactions and as a substrate for the citric acid, or tricarboxylic acid (TCA), cycle. The Human Immunodeficiency Virus type 1 (HIV-1) productively infects activated CD4+ T cells that are known to require glutamine for proliferation and for carrying out effector functions. As a virus, HIV-1 is furthermore entirely dependent on host metabolism to support its replication...
August 26, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28827112/design-synthesis-and-evaluation-of-substituted-nicotinamide-adenine-dinucleotide-nad-synthetase-inhibitors-as-potential-antitubercular-agents
#9
Xu Wang, Yong-Mo Ahn, Adam G Lentscher, Julia S Lister, Robert C Brothers, Malea M Kneen, Barbara Gerratana, Helena I Boshoff, Cynthia S Dowd
Nicotinamide adenine dinucleotide (NAD(+)) synthetase catalyzes the last step in NAD(+) biosynthesis. Depletion of NAD(+) is bactericidal for both active and dormant Mycobacterium tuberculosis (Mtb). By inhibiting NAD(+) synthetase (NadE) from Mtb, we expect to eliminate NAD(+) production which will result in cell death in both growing and nonreplicating Mtb. NadE inhibitors have been investigated against various pathogens, but few have been tested against Mtb. Here, we report on the expansion of a series of urea-sulfonamides, previously reported by Brouillette et al...
September 15, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28826492/environmental-cystine-drives-glutamine-anaplerosis-and-sensitizes-cancer-cells-to-glutaminase-inhibition
#10
Alexander Muir, Laura V Danai, Dan Y Gui, Chiara Y Waingarten, Caroline A Lewis, Matthew G Vander Heiden
Many mammalian cancer cell lines depend on glutamine as a major tri-carboxylic acid (TCA) cycle anaplerotic substrate to support proliferation. However, some cell lines that depend on glutamine anaplerosis in culture rely less on glutamine catabolism to proliferate in vivo. We sought to understand the environmental differences that cause differential dependence on glutamine for anaplerosis. We find that cells cultured in adult bovine serum, which better reflects nutrients available to cells in vivo, exhibit decreased glutamine catabolism and reduced reliance on glutamine anaplerosis compared to cells cultured in standard tissue culture conditions...
August 15, 2017: ELife
https://www.readbyqxmd.com/read/28813436/enhancement-of-the-production-of-l-glutaminase-an-anticancer-enzyme-from-aeromonas-veronii-by-adaptive-and-induced-mutation-techniques
#11
S Aravinth Vijay Jesuraj, Md Moklesur Rahman Sarker, Long Chiau Ming, S Marylin Jeya Praya, M Ravikumar, Wong Tin Wui
Microbial anti-cancer enzymes have been proven to be effective and economical agents for cancer treatment. Aeromonas veronii has been identified as a microorganism with the potential to produce L-glutaminase, an anticancer agent effective against acute lymphocytic leukaemia. In this study, a selective medium of Aeromonas veronii was used to culture the microorganism. Strain improvement was done by adaptive and induced mutational techniques. A selective minimal agar media was incorporated for the growth of the strain which further supports adaptive mutation...
2017: PloS One
https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#12
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28801829/cloning-and-characterization-of-halomonas-elongata-l-asparaginase-a-promising-chemotherapeutic-agent
#13
Ali Ghasemi, Sedigheh Asad, Mahboubeh Kabiri, Bahareh Dabirmanesh
L-asparaginase has been used in the treatment of patients with acute lymphoblastic leukemia (ALL) for more than 30 years. Rapid clearance of the enzyme from blood stream and its L-glutaminase-dependent neurotoxicity has led to searching for new L-asparaginases with more desirable properties. In the present study, L-asparaginase coding gene of Halomonas elongata was isolated, expressed in Escherichia coli, purified, and characterized. The purified protein was found to have a molecular mass of 39.5 kDa and 1000-folds more activity towards L-asparagine than L-glutamine...
August 11, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28800318/mir-513c-suppresses-neuroblastoma-cell-migration-invasion-and-proliferation-through-direct-targeting-glutaminase-gls
#14
Hong-Liang Xia, Yao Lv, Chun-Wei Xu, Ming-Cui Fu, Ting Zhang, Xiang-Ming Yan, Shu Dai, Qian-Wei Xiong, Yun Zhou, Jian Wang, Xu Cao
Neuroblastoma is a brain malignancy of childhood and accounts for 7-10% of childhood cancers, leading to approximately 15% of pediatric cancer deaths. MicroRNAs (miRNAs) are a family of short (about 18-25 nucleotides), noncoding and single stranded endogenous RNAs, which complementarily bind to the 3' untranslated regions of their target genes. Recently, glutamine metabolism has been recognized as an important nutrition source for tumor cells, and hence targeting glutamine metabolism could benefit to development of anti-cancer agents...
July 2, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28797105/regulation-of-hepatic-stellate-cell-proliferation-and-activation-by-glutamine-metabolism
#15
Jiang Li, Mohammed Ghazwani, Ke Liu, Yixian Huang, Na Chang, Jie Fan, Fengtian He, Liying Li, Shizhong Bu, Wen Xie, Xiaochao Ma, Song Li
Liver fibrosis is the excessive accumulation of extracellular matrix proteins, which is mainly caused by accumulation of activated hepatic stellate cells (HSCs). The mechanisms of activation and proliferation of HSCs, two key events after liver damage, have been studied for many years. Here we report a novel pathway to control HSCs by regulating glutamine metabolism. We demonstrated that the proliferation of HSCs is critically dependent on glutamine that is used to generate α-ketoglutarate (α-KG) and non-essential amino acid (NEAA)...
2017: PloS One
https://www.readbyqxmd.com/read/28775361/a-conserved-neuronal-daf-16-foxo-plays-an-important-role-in-conveying-pheromone-signals-to-elicit-repulsion-behavior-in-caenorhabditis-elegans
#16
Donha Park, Jeong-Hoon Hahm, Saeram Park, Go Ha, Gyeong-Eon Chang, Haelim Jeong, Heekyeong Kim, Sunhee Kim, Eunji Cheong, Young-Ki Paik
Animals use pheromones as a conspecific chemical language to respond appropriately to environmental changes. The soil nematode Caenorhabditis elegans secretes ascaroside pheromones throughout the lifecycle, which influences entry into dauer phase in early larvae, in addition to sexual attraction and aggregation. In adult hermaphrodites, pheromone sensory signals perceived by worms usually elicit repulsion as an initial behavioral signature. However, the molecular mechanisms underlying neuronal pheromone sensory process from perception to repulsion in adult hermaphrodites remain poorly understood...
August 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28770953/microrna-200c-exacerbates-the-ischemia-reperfusion-injury-of-heart-through-targeting-the-glutaminase-gls-mediated-glutamine-metabolism
#17
F Liu, Y Li, G Liu
OBJECTIVE: Cardiac ischemia and reperfusion, the common pathophysiological processes during cardiovascular surgery, are followed by oxidative stresses during the restoration of blood flow to the tissue, known as ischemia/reperfusion (IR) injury. microRNAs (miRNAs) are a group of endogenous, short and noncoding RNAs that post-transcriptionally repress their target mRNA expressions. Currently, the roles of microRNAs in the IR are still under investigated. This study will investigate the roles and mechanisms of miRNAs in the ischemia/reperfusion injury of the heart...
July 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28764932/adeno-associated-viral-serotypes-differentially-transduce-inhibitory-neurons-within-the-rat-amygdala
#18
C A de Solis, M P Hosek, R Holehonnur, A Ho, A Banerjee, J A Luong, L E Jones, D Chaturvedi, J E Ploski
Recombinant adeno-associated viruses (AAV) are frequently used to make localized genetic manipulations within the rodent brain. It is accepted that the different viral serotypes possess differing affinities for particular cell types, but it is not clear how these properties affect their ability to transduce specific neuronal cell sub-types. Here, we examined ten AAV serotypes for their ability to transduce neurons within the rat basal and lateral nuclei of the amygdala (BLA) and the central nucleus of the amygdala (CeA)...
July 29, 2017: Brain Research
https://www.readbyqxmd.com/read/28750681/drug-induced-amino-acid-deprivation-as-strategy-for-cancer-therapy
#19
REVIEW
Marcus Kwong Lam Fung, Godfrey Chi-Fung Chan
Cancer is caused by uncontrollable growth of neoplastic cells, leading to invasion of adjacent and distant tissues resulting in death. Cancer cells have specific nutrient(s) auxotrophy and have a much higher nutrient demand compared to normal tissues. Therefore, different metabolic inhibitors or nutrient-depleting enzymes have been tested for their anti-cancer activities. We review recent available laboratory and clinical data on using various specific amino acid metabolic pathways inhibitors in treating cancers...
July 27, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28671681/extracellular-vesicles-are-independent-metabolic-units-with-asparaginase-activity
#20
Nunzio Iraci, Edoardo Gaude, Tommaso Leonardi, Ana S H Costa, Chiara Cossetti, Luca Peruzzotti-Jametti, Joshua D Bernstock, Harpreet K Saini, Maurizio Gelati, Angelo Luigi Vescovi, Carlos Bastos, Nuno Faria, Luigi G Occhipinti, Anton J Enright, Christian Frezza, Stefano Pluchino
Extracellular vesicles (EVs) are membrane particles involved in the exchange of a broad range of bioactive molecules between cells and the microenvironment. Although it has been shown that cells can traffic metabolic enzymes via EVs, much remains to be elucidated with regard to their intrinsic metabolic activity. Accordingly, herein we assessed the ability of neural stem/progenitor cell (NSC)-derived EVs to consume and produce metabolites. Our metabolomics and functional analyses both revealed that EVs harbor L-asparaginase activity, catalyzed by the enzyme asparaginase-like protein 1 (Asrgl1)...
September 2017: Nature Chemical Biology
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