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https://www.readbyqxmd.com/read/28346230/glutaminase-and-poly-adp-ribose-polymerase-inhibitors-suppress-pyrimidine-synthesis-and-vhl-deficient-renal-cancers
#1
Arimichi Okazaki, Paulo A Gameiro, Danos Christodoulou, Laura Laviollette, Meike Schneider, Frances Chaves, Anat Stemmer-Rachamimov, Stephanie A Yazinski, Richard Lee, Gregory Stephanopoulos, Lee Zou, Othon Iliopoulos
Many cancer-associated mutations that deregulate cellular metabolic responses to hypoxia also reprogram carbon metabolism to promote utilization of glutamine. In renal cell carcinoma (RCC), cells deficient in the von Hippel-Lindau (VHL) tumor suppressor gene use glutamine to generate citrate and lipids through reductive carboxylation (RC) of α-ketoglutarate (αKG). Glutamine can also generate aspartate, the carbon source for pyrimidine biosynthesis, and glutathione for redox balance. Here we have shown that VHL-/- RCC cells rely on RC-derived aspartate to maintain de novo pyrimidine biosynthesis...
March 27, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28345452/l-glutamine-supplementation-promotes-an-improved-energetic-balance-in-walker-256-tumor-bearing-rats
#2
Heber Amilcar Martins, Roberto Barbosa Bazotte, Geraldo Emilio Vicentini, Mariana Machado Lima, Flavia Alessandra Guarnier, Catchia Hermes-Uliana, Flavia Cristina Vieira Frez, Gleison Daion Piovezana Bossolani, Luciane Fracaro, Larissa Dos Santos Fávaro, Mariana Inocêncio Manzano, Jacqueline Nelisis Zanoni
We evaluated the effects of supplementation with oral l-glutamine in Walker-256 tumor-bearing rats. A total of 32 male Wistar rats aged 54 days were randomly divided into four groups: rats without Walker-256 tumor, that is, control rats (C group); control rats supplemented with l-glutamine (CG group); Walker-256 tumor rats without l-glutamine supplementation (WT group); and WT rats supplemented with l-glutamine (WTG group). l-Glutamine was incorporated into standard food at a proportion of 2 g/100 g (2%). After 10 days of the experimental period, the jejunum and duodenum were removed and processed...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28345298/effects-of-t-loop-modification-on-the-pii-signaling-protein-structure-of-uridylylated-escherichia-coli-glnb-bound-to-atp
#3
Carles Palanca, Vicente Rubio
To adapt to environments with variable nitrogen sources and richness, the widely distributed homotrimeric PII signaling proteins bind their allosteric effectors ADP/ATP/2-oxoglutarate, and experience nitrogen-sensitive uridylylation of their flexible T-loops at Tyr51, regulating their interactions with effector proteins. To clarify whether uridylylation triggers a given T-loop conformation, we determined the crystal structure of the classical paradigm of PII protein, Escherichia coli GlnB (EcGlnB), in fully uridylylated form (EcGlnB-UMP3 )...
March 26, 2017: Environmental Microbiology Reports
https://www.readbyqxmd.com/read/28343468/glutamine-protects-rabbit-spermatozoa-against-oxidative-stress-via-glutathione-synthesis-during-cryopreservation
#4
Zhendong Zhu, Xiaoteng Fan, Yinghua Lv, Yan Lin, De Wu, Wenxian Zeng
Mammalian spermatozoa are extremely susceptible to high doses of reactive oxygen species (ROS). The aim of the present study was to investigate the potential role of glutamine in protecting rabbit spermatozoa against ROS stress during cryopreservation and post-thaw incubation. Freshly ejaculated semen was diluted with Tris-citrate-glucose extender supplemented with glutamine. The addition of 20mM glutamine significantly improved sperm motility, acrosome integrity, membrane integrity and mitochondrial activity...
March 27, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28342810/expression-and-putative-role-of-mitochondrial-transport-proteins-in-cancer
#5
REVIEW
Oleksandr Lytovchenko, Edmund R S Kunji
Cancer cells undergo major changes in energy and biosynthetic metabolism. One of them is the Warburg effect, in which pyruvate is used for fermentation rather for oxidative phosphorylation. Another major one is their increased reliance on glutamine, which helps to replenish the pool of Krebs cycle metabolites used for other purposes, such as amino acid or lipid biosynthesis. Mitochondria are central to these alterations, as the biochemical pathways linking these processes run through these organelles. Two membranes, an outer and inner membrane, surround mitochondria, the latter being impermeable to most organic compounds...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28342331/drought-stress-obliterates-the-preference-for-ammonium-as-an-n-source-in-the-c4-plant-spartina-alterniflora
#6
Kamel Hessini, Herbert J Kronzucker, Chedly Abdelly, Cristina Cruz
The C4 grass Spartina alterniflora is known for its unique salt tolerance and strong preference for ammonium (NH4(+)) as a nitrogen (N) source. We here examined whether Spartina's unique preference for NH4(+) results in improved performance under drought stress. Manipulative greenhouse experiments were carried out to measure the effects of variable water availability and inorganic N sources on plant performance (growth, photosynthesis, antioxidant, and N metabolism). Drought strongly reduced leaf number and area, plant fresh and dry weight, and photosynthetic activity on all N sources, but the reduction was most pronounced on NH4(+)...
March 9, 2017: Journal of Plant Physiology
https://www.readbyqxmd.com/read/28341660/the-noncoding-rna-linc-adamts5-cooperates-with-rreb1-to-protect-from-intervertebral-disc-degeneration-through-inhibiting-adamts5-expression
#7
Kun Wang, Yu Song, Wei Liu, Xinghuo Wu, Yukun Zhang, Shuai Li, Liang Kang, Ji Tu, Kangcheng Zhao, Wenbin Hua, Cao Yang
Previous studies have indicated the important roles of ADAMTS5 in intervertebral disc degeneration. However, the mechanisms that regulate ADAMTS5 expression in nuclear pulposus (NP) cells remain largely unknown. Evidence suggests that intergenic transcription may be associated with genes that encode transcriptional regulators. Here, we identified a long intergenic noncoding RNA, linc-ADAMTS5, that was transcribed in the opposite direction of ADAMTS5. In this study, through mining computational algorithm programs, and public available data sets, we identified Ras responsive element binding protein 1 (RREB1) as a crucial transcription factor regulating the expression of ADAMTS5 in NP cells...
March 24, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28340368/synthesis-molecular-docking-antimycobacterial-and-antimicrobial-evaluation-of-new-pyrrolo-3-2-c-pyridine-mannich-bases
#8
Gilish Jose, Tholappanavara H Suresha Kumara, Haliwana B V Sowmya, Dharmarajan Sriram, Tayur N Guru Row, Amar A Hosamani, Sunil S More, Bhavya Janardhan, B G Harish, Sandeep Telkar, Yalegara Siddappa Ravikumar
In this report, we describe the synthesis and biological evaluation of a new series of pyrrolo[3,2-c]pyridine Mannich bases (7a-v). The Mannich bases were obtained in good yields by one-pot three component condensation of pyrrolo[3,2-c]pyridine scaffold (6a-c) with secondary amines and excess of formaldehyde solution in AcOH. The chemical structures of the compounds were characterized by (1)H NMR, (13)C NMR, LC/MS and elemental analysis. Single crystal X-ray diffraction has been recorded for compound 7k ([C23H29ClN4](+2), H2O)...
March 16, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28339983/acr11-is-an-activator-of-plastid-type-glutamine-synthetase-gs2-in-arabidopsis-thaliana
#9
Takashi Osanai, Ayuko Kuwahara, Hitomi Otsuki, Kazuki Saito, Masami Yokota Hirai
Glutamine synthetase (GS) is an important enzyme for nitrogen assimilation, and GS2, encoded by GLN2, is the only plastid-type GS in Arabidopsis thaliana. A co-expression analysis suggested that the expression level of the gene encoding a uridylyltransferase-like protein, ACR11, is strongly correlated with GLN2 expression levels. Here we showed that the recombinant ACR11 protein increased GS2 activity in vitro by reducing the Km values of its substrate glutamine. A T-DNA insertion mutant of ACR11 exhibited a reduced GS activity under low nitrate conditions and reduced glutamine levels...
March 6, 2017: Plant & Cell Physiology
https://www.readbyqxmd.com/read/28338973/inflammation-autoimmunity-and-hypertension-the-essential-role-of-tissue-transglutaminase
#10
Chen Liu, Rodney E Kellems, Yang Xia
Inflammatory cytokines cause hypertension when introduced into animals. Additional evidence indicates that cytokines induce the production of autoantibodies that activate the AT1 angiotensin receptor (AT1R). Extensive evidence shows that these autoantibodies, termed AT1-AA, contribute to hypertension. We review here recent studies showing that cytokine-induced hypertension and AT1-AA production require the ubiquitous enzyme, tissue transglutaminase (TG2). We consider 3 mechanisms by which TG2 may contribute to hypertension...
March 13, 2017: American Journal of Hypertension
https://www.readbyqxmd.com/read/28336748/the-sweet-side-of-ampk-signaling-regulation-of-gfat1
#11
John W Scott, Jonathan S Oakhill
Maintaining a steady balance between nutrient supply and energy demand is essential for all living organisms and is achieved through the dynamic control of metabolic processes that produce and consume adenosine-5'-triphosphate (ATP), the universal currency of energy in all cells. A key sensor of cellular energy is the adenosine-5'-monophosphate (AMP)-activated protein kinase (AMPK), which is the core component of a signaling network that regulates energy and nutrient metabolism. AMPK is activated by metabolic stresses that decrease cellular ATP, and functions to restore energy balance by orchestrating a switch in metabolism away from anabolic pathways toward energy-generating catabolic processes...
March 23, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28336567/sox9-is-an-astrocyte-specific-nuclear-marker-in-the-adult-brain-outside-the-neurogenic-regions
#12
Wei Sun, Adam Cornwell, Jiashu Li, Sisi Peng, M Joana Osorio, Nadia Aalling Su Wanga, Abdellatif Benraiss, Nanhong Lou, Steven A Goldman, Maiken Nedergaard
Astrocytes have in recent years become the focus of intense experimental interest, yet markers for their definitive identification remain both scarce and imperfect. Astrocytes may be recognized as such by their expression of glial fibrillary acidic protein (GFAP), glutamine synthetase (GS), glutamate transporter 1 (GLT1)quaporin-4 (AQP4)ldehyde dehydrogenase 1 family member L1 (ALDH1L1)nd other proteins. Yet these proteins may all be regulated both developmentally and functionally, restricting their utility...
March 23, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28336547/glycans-in-the-intestinal-peptide-transporter-pept1-contribute-to-function-and-protect-from-proteolysis
#13
Tamara Stelzl, Kerstin Elisabeth Geillinger-Kästle, Jürgen Stolz, Hannelore Daniel
Despite the fact that many membrane proteins carry extracellular glycans, little is known about whether the glycan chains also affect protein function. We recently demonstrated that the proton-coupled oligopeptide transporter 1 (PEPT1) in the intestine is glycosylated at six asparagine residues (N50, N406, N439, N510, N515, N532). Mutagenesis-induced disruption of the individual N-glycosylation site N50, which is highly conserved among mammals, was detected to significantly enhance the PEPT1 mediated inward transport of peptides...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28336107/enriched-enteral-nutrition-may-improve-short-term-survival-in-stage-iv-gastric-cancer-patients-a-randomized-controlled-trial
#14
Stanislaw Klek, Lucyna Scislo, Elzbieta Walewska, Ryszard Choruz, Aleksander Galas
OBJECTIVE: The aim of the study was to determine whether the postoperative use of enteral nutrition enriched with arginine, glutamine, and omega-3 fatty acids influences survival in patients diagnosed with stomach cancer. For the purpose of the study, the second wave of the trial performed in 2003 to 2009 was done. METHODS: Ninety-nine patients who underwent surgery for gastric cancer (27 F, 72 M, mean age: 62.9 y) met the inclusion criteria. Of those, 54 were randomized to standard and 45 to enriched enteral nutrition (EEN)...
April 2017: Nutrition
https://www.readbyqxmd.com/read/28335103/correlation-between-gastric-emptying-and-gastric-adaptive-relaxation-influenced-by-amino-acids
#15
Masayuki Uchida, Orie Kobayashi, Chizuru Saito
Background/Aims: Amino acids have many physiological activities. We report the correlation between gastric emptying and gastric adaptive relaxation using tryptophan and amino acids with a straight alkyl chain, hydroxylated chain, and branched chain. Here we sought to further clarify the correlation between gastric emptying and gastric adaptive relaxation by using other amino acids. Methods: In Sprague-Dawley rats, gastric emptying was evaluated by a breath test using [1-¹³C] acetic acid...
March 23, 2017: Journal of Neurogastroenterology and Motility
https://www.readbyqxmd.com/read/28334434/withdrawn-nutrition-support-for-bone-marrow-transplant-patients
#16
REVIEW
Susan M Murray, Sima Pindoria
BACKGROUND: This is an update of the original Cochrane review published in Issue 2, 2002. Bone marrow transplantation involves administration of toxic chemotherapy and infusion of marrow cells. After treatment, patients can develop poor appetite, mucositis and gastrointestinal failure, leading to malnutrition. To prevent this, parenteral nutrition (PN) support is often first choice but is associated with increased risk of infection. Enteral nutrition (EN) is an alternative, as is addition of substrates...
March 23, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28333211/glutathione-affects-the-transport-activity-of-rhizobium-leguminosarum-3841-and-is-essential-for-efficient-nodulation
#17
Guojun Cheng, Ramakrishnan Karunakaran, Alison K East, Olaya Munoz-Azcarate, Philip S Poole
As glutathione (GSH) plays an essential role in growth and symbiotic capacity of rhizobia, a glutathione synthetase (gshB) mutant of Rhizobium leguminosarum biovar viciae 3841 (Rlv3841) was characterised. It fails to efficiently utilise various compounds as a sole carbon source, including glucose, succinate, glutamine and histidine, and shows 60-69% reduction in uptake rates of glucose, succinate and the non-metabolisable substrate α-amino isobutyric acid (AIB). The defect in glucose uptake can be overcome by addition of exogenous GSH, indicating GSH, but not its bacterial synthesis, is required for efficient transport...
February 23, 2017: FEMS Microbiology Letters
https://www.readbyqxmd.com/read/28333144/aberrant-ipsc-derived-human-astrocytes-in-alzheimer-s-disease
#18
V C Jones, R Atkinson-Dell, A Verkhratsky, L Mohamet
The pathological potential of human astroglia in Alzheimer's disease (AD) was analysed in vitro using induced pluripotent stem cell (iPSC) technology. Here, we report development of a human iPSC-derived astrocyte model created from healthy individuals and patients with either early-onset familial AD (FAD) or the late-onset sporadic form of AD (SAD). Our chemically defined and highly efficient model provides >95% homogeneous populations of human astrocytes within 30 days of differentiation from cortical neural progenitor cells (NPCs)...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28331060/proximal-tubule-glutamine-synthetase-expression-is-necessary-for-the-normal-response-to-dietary-protein-restriction
#19
Hyun-Wook Lee, Gunars Osis, Mary E Handlogten, Jill W Verlander, I David Weiner
Dietary protein restriction has multiple benefits in kidney disease. Because protein intake is a major determinant of endogenous acid production, it is important that net acid excretion change in parallel during changes in dietary protein intake. Dietary protein restriction decreases endogenous acid production and ¬decreases urinary ammonia excretion, a major component of net acid excretion. Glutamine synthetase (GS) catalyzes the reaction of NH4+ and glutamate, which regenerates the essential amino acid glutamine and decreases net ammonia generation...
March 22, 2017: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/28330181/optimization-of-medium-composition-for-in-vitro-shoot-proliferation-and-growth-of-date-palm-cv-mejhoul
#20
Mouaad Amine Mazri, Reda Meziani, Jamal El Fadile, Az-Eddine Ezzinbi
The effects of major mineral salts, L-glutamine, myo-inositol and carbon source on shoot bud proliferation of date palm (Phoenix dactylifera L.) cv. Mejhoul were evaluated. Different concentrations of ammonium nitrate (NH4NO3; 550, 825 or 1650 mg/L), potassium nitrate (KNO3; 633.3, 950 or 1900 mg/L), calcium chloride dehydrate (CaCl2·2H2O; 147, 220 or 440 mg/L), potassium dihydrogen phosphate (KH2PO4; 57, 85 or 170 mg/L), magnesium sulfate heptahydrate (MgSO4·7H2O; 123, 185 or 370 mg/L), L-glutamine and myo-inositol (0...
June 2016: 3 Biotech
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