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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
#1
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/28109906/succinate-in-the-cancer-immune-cycle
#2
Shuai Jiang, Wei Yan
Succinate is an important intermediate of the tricarboxylic acid (TCA) cycle. In mitochondria, it plays a crucial role in generating adenosine triphosphate. Succinate metabolism is also intertwined with the metabolism of other metabolites and with the "GABA shunt" of the glutamine pathway. Recently, it has become increasingly apparent that the roles of succinate extend into the realms of immunity and cancer. Succinate is a key modulator of the hypoxic response, an important player in tumorigenesis; succinate is also involved in protein succinylation, a novel posttranslational modification pathway...
January 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28109606/short-communication-glutamine-modulates-inflammatory-responses-to-lipopolysaccharide-in-ex-vivo-bovine-endometrium
#3
Pablo G Noleto, João Paulo E Saut, I Martin Sheldon
Bacteria infect the endometrium lining the uterus of cattle after parturition, and clearance of these microbes depends on a robust innate immune response to bacterial molecules, such as the endotoxin lipopolysaccharide (LPS). Endometrial inflammation is characterized by secretion of the cytokines IL-1β and IL-6 and the chemokine IL-8. However, animals often fail to clear invading bacteria and develop uterine disease if they are in negative energy balance, with reduced abundance of glucose and glutamine, which are substrates for energy in tissues...
January 18, 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/28109537/clinical-factors-associated-with-cerebral-metabolism-in-term-neonates-with-congenital-heart-disease
#4
Anna Lonyai Harbison, Jodie K Votava-Smith, Sylvia Del Castillo, S Ram Kumar, Vince Lee, Vincent Schmithorst, Hollie A Lai, Sharon O'Neil, Stefan Bluml, Lisa Paquette, Ashok Panigrahy
OBJECTIVE: To determine associations between patient and clinical factors with postnatal brain metabolism in term neonates with congenital heart disease (CHD) via the use of quantitative magnetic resonance spectroscopy. STUDY DESIGN: Neonates with CHD were enrolled prospectively to undergo pre- and postoperative 3T brain magnetic resonance imaging. Short-echo single-voxel magnetic resonance spectroscopy of parietal white matter was used to quantify metabolites related to brain maturation (n-acetyl aspartate, choline, myo- inositol), neurotransmitters (glutamate and gamma-aminobutyric acid), energy metabolism (glutamine, citrate, glucose, and phosphocreatine), and injury/apoptosis (lactate and lipids)...
January 19, 2017: Journal of Pediatrics
https://www.readbyqxmd.com/read/28109177/glutamine-synthetase-stabilizes-the-binding-of-glnr-to-nitrogen-fixation-gene-operators
#5
Gabriela de Carvalho Fernandes, Ksenia Hauf, Fernando Hayashi Sant'Anna, Karl Forchhammer, Luciane Maria Pereira Passaglia
Biological nitrogen fixation (BNF) is a high energy demanding process carried out by diazotrophic microorganisms that supply combined nitrogen to the biosphere. The genes related to BNF are strictly regulated, but these mechanisms are poorly understood in Gram-positive bacteria. The transcription factor GlnR was proposed to regulate nitrogen fixation related genes based on Paenibacillus comparative genomics. In order to validate this proposal, we investigated BNF regulatory sequences in Paenibacillus riograndensis SBR5(T) genome...
January 21, 2017: FEBS Journal
https://www.readbyqxmd.com/read/28106079/modification-of-tumour-cell-metabolism-modulates-sensitivity-to-chk1-inhibitor-induced-dna-damage
#6
Andrew J Massey
Chk1 kinase inhibitors are currently under clinical investigation as potentiators of cytotoxic chemotherapy and demonstrate potent activity in combination with anti-metabolite drugs that increase replication stress through the inhibition of nucleotide or deoxyribonucleotide biosynthesis. Inhibiting other metabolic pathways critical for the supply of building blocks necessary to support DNA replication may lead to increased DNA damage and synergy with an inhibitor of Chk1. A screen of small molecule metabolism modulators identified combinatorial activity between a Chk1 inhibitor and chloroquine or the LDHA/LDHB inhibitor GSK 2837808A...
January 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28105083/effects-of-glutamine-on-markers-of-intestinal-inflammatory-response-and-mucosal-permeability-in-abdominal-surgery-patients-a-meta-analysis
#7
Xiao-Liang Shu, Ting-Ting Yu, Kai Kang, Jian Zhao
The present meta-analysis was carried out to determine whether supplementation with glutamine (Gln) would reduce the intestinal inflammatory response and mucosal permeability in patients undergoing abdominal surgery. The PubMed, EMBASE, Web of Science, and The Cochrane Library databases were searched for randomized controlled trials on the effects of supplementation with Gln, and published from August, 1966 to June 2014. Inclusion criteria for the meta-analysis were: i) Study design was a randomized controlled trial, ii) study included patients undergoing abdominal surgery, iii) study patients received a supplementation with Gln peptide (Ala-Gln or Gly-Gln) whereas control patients did not use any supplements, and iv) study outcomes included inflammatory markers [C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), and interleukin (IL)-6, and IL-2 receptor] and markers of intestinal permeability [lactulose/mannitol, diamine oxidase, D(-)lactic acid, and endotoxin]...
December 2016: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28104554/abnormalities-in-metabolite-concentrations-in-tourette-s-disorder-and-obsessive-compulsive-disorder-a-proton-magnetic-resonance-spectroscopy-study
#8
Siyan Fan, Danielle C Cath, Odile A van den Heuvel, Ysbrand D van der Werf, Caroline Schöls, Dick J Veltman, Petra J W Pouwels
INTRODUCTION: Abnormal glutamatergic transmission in cortico-striato-thalamo-cortical (CSTC) circuits is thought to be involved in the pathophysiology of Tourette's disorder (TD) and obsessive-compulsive disorder (OCD). Using proton magnetic resonance spectroscopy, the current study aimed to investigate regional concentrations of glutamatergic compounds in TD and OCD patients in comparison to healthy control subjects (HC). MATERIAL AND METHODS: Twenty-three TD patients, 20 OCD patients and 22 HC were included...
January 4, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28104249/il-17-signalling-in-astrocytes-promotes-glutamate-excitotoxicity-indications-for-the-link-between-inflammatory-and-neurodegenerative-events-in-multiple-sclerosis
#9
Milos Kostic, Nikola Zivkovic, Ana Cvetanovic, Ivana Stojanovic, Miodrag Colic
OBJECTIVE: Th-17 cells have been exclusively referred to inflammatory events in multiple sclerosis (MS), while their importance in the development of glutamate excitotoxicity and the consequent neurodegeneration has been a completely unexplored concept. Accordingly, the objective of our study was to assess IL-17A effect on astrocyte ability to metabolize and release glutamate, considering that astrocytes had the central role in glutamate homeostasis. METHODS: By using primary rat astrocyte cultures, astrocyte ability to uptake glutamate was estimated by the alterations of glutamate transporters (GLAST and GLT-1) expression, whereas changes in glutamine synthetase expression were used to estimate the ability to metabolize glutamate...
January 2017: Multiple Sclerosis and related Disorders
https://www.readbyqxmd.com/read/28103400/the-sufbc2-d-complex-is-required-for-the-biogenesis-of-all-major-classes-of-plastid-fe-s-proteins
#10
Xueyun Hu, Yukako Kato, Akihiro Sumida, Ayumi Tanaka, Ryouichi Tanaka
Iron-sulfur (Fe-S) proteins play crucial roles in plastids, participating in photosynthesis and other metabolic pathways. Fe-S clusters are thought to be assembled on a scaffold complex composed of SUFB, SUFC and SUFD proteins. However, several additional proteins provide putative scaffold functions in plastids, and, therefore, the contribution of SUFB, C and D proteins to overall Fe-S assembly still remains unclear. In order to gain insights regarding Fe-S cluster biosynthesis in plastids, we analyzed the complex composed of SUFB, C and D in Arabidopsis by blue-native polyacrylamide gel electrophoresis...
January 19, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28102753/chloroplastic-iron-sulfur-scaffold-protein-nfu3-is-essential-to-overall-plant-fitness
#11
Krishna Nath, James P O'Donnell, Yan Lu
A previous study showed that Nitrogen-Fixing-subunit-U-type protein NFU3 may act an iron-sulfur scaffold protein in the assembly and transfer of 4Fe-4S and 3Fe-4S clusters in the chloroplast. Examples of 4Fe-4S and 3Fe-4S-requiring proteins and complexes include Photosystem I (PSI), NAD(P)H dehydrogenase, and ferredoxin-dependent glutamine oxoglutarate aminotransferases. In this paper, the authors provided additional evidence for the role of NFU3 in 4Fe-4S and 3Fe-4S cluster assembly and transfer, as well as its role in overall plant fitness...
January 19, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28100770/control-of-amino-acid-homeostasis-by-a-ubiquitin-ligase-coactivator-protein-complex
#12
Damian Guerra, Sonia M Chapiro, Réjane Pratelli, Shi Yu, Weitao Jia, Julie Leary, Guillaume Pilot, Judy Callis
Intercellular amino acid transport is essential for the growth of all multicellular organisms, and its dysregulation is implicated in developmental disorders. By an unknown mechanism, amino acid efflux is stimulated in plants by over-expression of a membrane-localized protein (GLUTAMINE DUMPER 1, GDU1) that requires a ubiquitin ligase (LOSS OF GDU 2, LOG2). Here we further explore the physiological consequences of the interaction between these two proteins. LOG2 ubiquitin ligase activity is necessary for GDU1-dependent tolerance to exogenous amino acids, and LOG2 self-ubiquitination was markedly stimulated by the GDU1 cytosolic domain, suggesting that GDU1 functions as an adaptor or coactivator of amino acid exporter(s)...
January 18, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28099841/targeted-inhibition-of-egfr-and-glutaminase-induces-metabolic-crisis-in-egfr-mutant-lung-cancer
#13
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/28098946/negative-association-between-mr-spectroscopic-glutamate-markers-and-gray-matter-volume-after-alcohol-withdrawal-in-the-hippocampus-a-translational-study-in-humans-and-rats
#14
Ulrich Frischknecht, Derik Hermann, Nuran Tunc-Skarka, Guo-Ying Wang, Markus Sack, Julia van Eijk, Traute Demirakca, Claudia Falfan-Melgoza, Bertram Krumm, Sandra Dieter, Rainer Spanagel, Falk Kiefer, Karl F Mann, Wolfgang H Sommer, Gabriele Ende, Wolfgang Weber-Fahr
BACKGROUND: Both chronic alcohol consumption and alcohol withdrawal lead to neural tissue damage which partly recovers during abstinence. This study investigated withdrawal-associated changes in glutamatergic compounds, markers of neuronal integrity, and gray matter volumes during acute alcohol withdrawal in the hippocampus, a key region in development and maintenance of alcohol dependence in humans and rats. METHODS: Alcohol-dependent patients (N = 39) underwent magnetic resonance imaging (MRI) and MR spectroscopy (MRS) measurements within 24 hours after the last drink and after 2 weeks of abstinence...
January 18, 2017: Alcoholism, Clinical and Experimental Research
https://www.readbyqxmd.com/read/28098776/distinguishing-benign-from-malignant-pancreatic-and-periampullary-lesions-using-combined-use-of-%C3%A2-h-nmr-spectroscopy-and-gas-chromatography-mass-spectrometry
#15
Yarrow J McConnell, Farshad Farshidfar, Aalim M Weljie, Karen A Kopciuk, Elijah Dixon, Chad G Ball, Francis R Sutherland, Hans J Vogel, Oliver F Bathe
Previous work demonstrated that serum metabolomics can distinguish pancreatic cancer from benign disease. However, in the clinic, non-pancreatic periampullary cancers are difficult to distinguish from pancreatic cancer. Therefore, to test the clinical utility of this technology, we determined whether any pancreatic and periampullary adenocarcinoma could be distinguished from benign masses and biliary strictures. Sera from 157 patients with malignant and benign pancreatic and periampullary lesions were analyzed using proton nuclear magnetic resonance (¹H-NMR) spectroscopy and gas chromatography-mass spectrometry (GC-MS)...
January 13, 2017: Metabolites
https://www.readbyqxmd.com/read/28097679/abnormal-levels-of-seven-amino-neurotransmitters-in-depression-rat-brain-and-determination-by-hplc-fld
#16
Ting Cui, Hong-Mei Qiu, Dan Huang, Qi-Xin Zhou, Xiao-Yan Fu, Hai-Yan Li, Xin-Hui Jiang
The determination of amino acids with the actions-like neurotransmitters or modulators have been increasingly important for diagnose in many neuropsychiatric diseases. A rapid and simple high performance liquid chromatography with fluorescence detection (HPLC-FLD) was developed for simultaneous determination of seven amino acids: aspartate (Asp), glutamate (Glu), serine (Ser), glutamine (Gln), glycine (Gly), taurine (Tau) and γ-aminobutyric acid (GABA). Homoserine (Hse) was used as an internal standard (IS)...
January 18, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28097538/the-role-of-glutamine-synthetase-in-energy-production-and-glutamine-metabolism-during-oxidative-stress
#17
Nohaiah Aldarini, Azhar A Alhasawi, Sean C Thomas, Vasu D Appanna
Oxidative stress is known to severely impede aerobic adenosine triphosphate (ATP) synthesis. However, the metabolically-versatile Pseudomonas fluorescens survives this challenge by invoking alternative ATP-generating networks. When grown in a medium with glutamine as the sole organic nutrient in the presence of H2O2, the microbe utilizes glutamine synthetase (GS) to modulate its energy budget. The activity of this enzyme that mediates the release of energy stored in glutamine was sharply increased in the stressed cells compared to the controls...
January 17, 2017: Antonie Van Leeuwenhoek
https://www.readbyqxmd.com/read/28097474/igf-1r-regulates-the-extracellular-level-of-active-mmp-2-pathological-neovascularization-and-functionality-in-retinas-of-oir-mouse-model
#18
Valeria E Lorenc, Paula V Subirada Caldarone, María C Paz, Darío G Ferrer, José D Luna, Gustavo A Chiabrando, María C Sánchez
In ischemic proliferative diseases such as retinopathies, persistent hypoxia leads to the release of numerous neovascular factors that participate in the formation of abnormal vessels and eventually cause blindness. The upregulation and activation of metalloproteinases (MMP-2 and MMP-9) represent a final common pathway in this process. Although many regulators of the neovascular process have been identified, the complete role of the insulin-like growth factor 1 (IGF-1) and its receptor (IGF-1R) appears to be significantly more complex...
January 17, 2017: Molecular Neurobiology
https://www.readbyqxmd.com/read/28096492/identification-of-glutaminyl-cyclase-genes-involved-in-pyroglutamate-modification-of-fungal-lignocellulolytic-enzymes
#19
Vincent W Wu, Craig M Dana, Anthony T Iavarone, Douglas S Clark, N Louise Glass
: The breakdown of plant biomass to simple sugars is essential for the production of second-generation biofuels and high-value bioproducts. Currently, enzymes produced from filamentous fungi are used for deconstructing plant cell wall polysaccharides into fermentable sugars for biorefinery applications. A post-translational N-terminal pyroglutamate modification observed in some of these enzymes occurs when N-terminal glutamine or glutamate is cyclized to form a five-membered ring. This modification has been shown to confer resistance to thermal denaturation for CBH-1 and EG-1 cellulases...
January 17, 2017: MBio
https://www.readbyqxmd.com/read/28096245/prion-like-characteristics-of-polyglutamine-containing-proteins
#20
Margaret M P Pearce, Ron R Kopito
Transmissible spongiform encephalopathies are infectious neurodegenerative diseases caused by the conversion of prion protein (PrP) into a self-replicating conformation that spreads via templated conversion of natively folded PrP molecules within or between cells. Recent studies provide compelling evidence that prion-like behavior is a general property of most protein aggregates associated with neurodegenerative diseases. Many of these disorders are associated with spontaneous protein aggregation, but genetic mutations can increase the aggregation propensity of specific proteins, including expansion of polyglutamine (polyQ) tracts, which is causative of nine inherited neurodegenerative diseases...
January 17, 2017: Cold Spring Harbor Perspectives in Medicine
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