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https://www.readbyqxmd.com/read/28439409/serial-deletion-reveals-structural-basis-and-stability-for-the-core-enzyme-activity-of-human-glutaminase-1-isoforms-relevance-to-excitotoxic-neurodegeneration
#1
Yuju Li, Justin Peer, Runze Zhao, Yinghua Xu, Beiqing Wu, Yi Wang, Changhai Tian, Yunlong Huang, Jialin Zheng
BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28439016/astrocytes-locally-translate-transcripts-in-their-peripheral-processes
#2
Kristina Sakers, Allison M Lake, Rohan Khazanchi, Rebecca Ouwenga, Michael J Vasek, Adish Dani, Joseph D Dougherty
Local translation in neuronal processes is key to the alteration of synaptic strength necessary for long-term potentiation, learning, and memory. Here, we present evidence that regulated de novo protein synthesis occurs within distal, perisynaptic astrocyte processes. Astrocyte ribosomal proteins are found adjacent to synapses in vivo, and immunofluorescent detection of peptide elongation in acute slices demonstrates robust translation in distal processes. We have also developed a biochemical approach to define candidate transcripts that are locally translated in astrocyte processes...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438991/differentiation-of-v2a-interneurons-from-human-pluripotent-stem-cells
#3
Jessica C Butts, Dylan A McCreedy, Jorge Alexis Martinez-Vargas, Frederico N Mendoza-Camacho, Tracy A Hookway, Casey A Gifford, Praveen Taneja, Linda Noble-Haeusslein, Todd C McDevitt
The spinal cord consists of multiple neuronal cell types that are critical to motor control and arise from distinct progenitor domains in the developing neural tube. Excitatory V2a interneurons in particular are an integral component of central pattern generators that control respiration and locomotion; however, the lack of a robust source of human V2a interneurons limits the ability to molecularly profile these cells and examine their therapeutic potential to treat spinal cord injury (SCI). Here, we report the directed differentiation of CHX10(+) V2a interneurons from human pluripotent stem cells (hPSCs)...
April 24, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28438014/characterization-of-a-glutamate-decarboxylase-gad-from-enterococcus-avium-m5-isolated-from-jeotgal-a-fermented-korean-sea-food
#4
Kang Wook Lee, Jae Min Shim, Zhuang Yao, Jeong A Kim, Hyun-Jin Kim, Jeong Hwan Kim
To develop starters for the production of functional foods or materials, lactic acid bacteria producing γ-aminobutyric acid (GABA) were screened from jeotgals, Korean fermented sea foods. One isolate producing high amount of GABA from monosodium L-glutamate (MSG) was identified as Enterococcus avium by 16S rRNA gene sequencing. E. avium M5 produced 18.47 ± 1.26 mg/ml GABA when incubated for 48 h at 37°C in MRS broth with MSG (3%, w/v). A gadB gene encoding glutamate decarboxylase (GAD) was cloned and overexpressed in E...
April 25, 2017: Journal of Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28436326/evaluation-and-characterization-of-nutritive-properties-of-the-jelly-ear-culinary-medicinal-mushroom-auricularia-auricula-judae-agaricomycetes-from-nigeria
#5
Reginald Chibueze Ohiri, Essien Eka Bassey
This study investigated the nutritive properties of the culinary-medicinal mushroom Auricularia auricula- judae. From the analysis, among the major minerals, potassium was found in the highest concentration, with a value of 172.03 ± 8.62 mg/kg, whereas manganese had the highest concentration among trace elements, with a value of 1.66 ± 0.11 mg/kg. Glutamic acid was the amino acid detected in the largest amounts in this study, with a value of 10.09 ± 1.86 mg/kg. Although glutamine and asparagine were not detected in this mushroom, cysteine and methionine had the lowest concentrations, with values of 0...
2017: International Journal of Medicinal Mushrooms
https://www.readbyqxmd.com/read/28434875/covalent-protein-labeling-at-glutamic-acids
#6
Pablo Martín-Gago, Eyad K Fansa, Michael Winzker, Sandip Murarka, Petra Janning, Carsten Schultz-Fademrecht, Matthias Baumann, Alfred Wittinghofer, Herbert Waldmann
Covalent labeling of amino acids in proteins by reactive small molecules, in particular at cysteine SH and lysine NH groups, is a powerful approach to identify and characterize proteins and their functions. However, for the less-reactive carboxylic acids present in Asp and Glu, hardly any methodology is available. Employing the lipoprotein binding chaperone PDE6δ as an example, we demonstrate that incorporation of isoxazolium salts that resemble the structure and reactivity of Woodward's reagent K into protein ligands provides a novel method for selective covalent targeting of binding site carboxylic acids in whole proteomes...
April 13, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28432550/estradiol-mitigates-ischemia-reperfusion-induced-acute-renal-failure-through-nmda-receptor-antagonism-in-rats
#7
Amrit Pal Singh, Nirmal Singh, Preet Mohinder Singh Bedi
In the present study, we investigated possible involvement of N-methyl-D-aspartate receptors (NMDAR) in estradiol mediated protection against ischemia reperfusion (I/R)-induced acute renal failure (ARF) in rats. Bilateral renal ischemia of 40 min followed by reperfusion for 24 h induced ARF in male wistar rats. Quantification of serum creatinine, creatinine clearance (CrCl), blood urea nitrogen (BUN), uric acid, potassium, fractional excretion of sodium (FeNa), and urinary microproteins was done to assess I/R-induced renal damage in rats...
April 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28432493/effect-of-pharmacological-modulation-of-activity-of-metabotropic-glutamate-receptors-on-their-gene-expression-after-excitotoxic-damage-in-hippocampal-neurons
#8
E V Pershina, M V Kapralova, V I Arkhipov
Microinjection of kainic acid into rat hippocampus causes excitotoxic neuronal damage predominantly in the CA3 and CA1 fields. These lesions can be significantly reduced by simultaneous administration of MPEP, a negative allosteric modulator of type 5 metabotropic glutamate receptors, and LY354740, an agonist of type 2 metabotropic glutamate receptors. The decrease in neuronal death in the hippocampus during pharmacological modulation was paralleled by adaptive changes in gene expression. In the hippocampus, gene expression of type 5 postsynaptic metabotropic glutamate receptor was close to the control level, and in the frontal cortex expression of the gene of α1-subunit of the GABAA receptor returned to normal...
April 22, 2017: Bulletin of Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28431974/unique-mitochondrial-localization-of-arginase-1-and-2-in-hepatocytes-of-air-breathing-walking-catfish-clarias-batrachus-and-their-differential-expression-patterns-under-hyper-ammonia-stress
#9
Bodhisattwa Banerjee, Debaprasad Koner, Priyanka Lal, Nirmalendu Saha
Arginase (ARG) catalyzes the final step of ornithine-urea cycle (OUC) leading to a conversion of L-arginine to L-ornithine and urea. Several isoforms of ARG have been reported in vertebrates, out of which the two predominant isoforms are the cytosolic ARG1 and the mitochondrial ARG2. The air-breathing walking catfish (Clarias batrachus) is frequently being challenged by different environmental insults such as hyper-ammonia, dehydration and osmotic stresses in their natural habitats throughout the year. The present study investigated the active presence of ARG1 and ARG2 isoforms in hepatocytes along with unique localization of both the isoforms inside the mitochondria, and also their specific expression patterns under hyper-ammonia stress (5mM NH4Cl) in isolated hepatocytes of walking catfish...
April 18, 2017: Gene
https://www.readbyqxmd.com/read/28431930/quantitative-proteomics-reveals-key-proteins-regulated-by-eicosapentaenoic-acid-in-endothelial-activation
#10
Lu Zhang, Kunhong Xiao, Xuyang Zhao, Xiaoli Sun, Jianshu Zhang, Xian Wang, Yi Zhu, Xu Zhang
Eicosapentaenoic acid (EPA), an n-3 polyunsaturated fatty acid (PUFA), has been shown to decrease the risk of atherosclerosis by attenuating endothelial activation. In this study, we used mass spectrometry-based label-free quantitative proteomics to study the protective mechanisms of EPA and to identify key proteins that regulated by EPA in endothelial activation. Arachidonic acid (AA) was used as a control. HUVECs were pretreated with each of the two PUFAs, and then stimulated with TNFα as a model of endothelial activation...
April 18, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28431321/atherogenicity-of-amino-acids-in-the-lipid-laden-macrophage-model-system-in-vitro-and-in-atherosclerotic-mice-a-key-role-for-triglyceride-metabolism
#11
Oren Rom, Claudia Grajeda-Iglesias, Mahmoud Najjar, Niroz Abu-Saleh, Nina Volkova, Dalit Esther Dar, Tony Hayek, Michael Aviram
Atherosclerosis-related research has focused mainly on the effects of lipids on macrophage foam cell formation and atherogenesis, whereas the role of amino acids (AAs) was understudied. The current study aimed to identify anti- or pro-atherogenic AA in the macrophage model system and to elucidate the underlying metabolic and molecular mechanisms. J774A.1 cultured macrophages were treated with increasing concentrations of each 1 of the 20 AAs. Macrophage atherogenicity was assessed in terms of cellular toxicity, generation of reactive oxygen species (ROS) and cellular cholesterol or triglyceride content...
April 6, 2017: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/28430781/an-unmodified-wobble-uridine-in-trnas-specific-for-glutamine-lysine-and-glutamic-acid-from-salmonella-enterica-serovar-typhimurium-results-in-nonviability-due-to-increased-missense-errors
#12
Kristina Nilsson, Gunilla Jäger, Glenn R Björk
In the wobble position of tRNAs specific for Gln, Lys, and Glu a universally conserved 5-methylene-2-thiouridine derivative (xm5s2U34, x denotes any of several chemical substituents and 34 denotes the wobble position) is present, which is 5-(carboxy)methylaminomethyl-2-thiouridine ((c)mnm5s2U34) in Bacteria and 5-methylcarboxymethyl-2-thiouridine (mcm5s2U34) in Eukarya. Here we show that mutants of the bacterium Salmonella enterica Serovar Typhimurium LT2 lacking either the s2- or the (c)mnm5-group of (c)mnm5s2U34 grow poorly especially at low temperature and do not grow at all at 15°C in both rich and glucose minimal media...
2017: PloS One
https://www.readbyqxmd.com/read/28430183/neuroprotectin-d1-upregulates-iduna-expression-and-provides-protection-in-cellular-uncompensated-oxidative-stress-and-in-experimental-ischemic-stroke
#13
Ludmila Belayev, Pranab K Mukherjee, Veronica Balaszczuk, Jorgelina M Calandria, Andre Obenaus, Larissa Khoutorova, Sung-Ha Hong, Nicolas G Bazan
Ring finger protein 146 (Iduna) facilitates DNA repair and protects against cell death induced by NMDA receptor-mediated glutamate excitotoxicity or by cerebral ischemia. Neuroprotectin D1 (NPD1), a docosahexaenoic acid (DHA)-derived lipid mediator, promotes cell survival under uncompensated oxidative stress (UOS). Our data demonstrate that NPD1 potently upregulates Iduna expression and provides remarkable cell protection against UOS. Iduna, which was increased by the lipid mediator, requires the presence of the poly(ADP-ribose) (PAR) sites...
April 21, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28429309/%C3%AE-ketoadipic-acid-and-%C3%AE-aminoadipic-acid-cause-disturbance-of-glutamatergic-neurotransmission-and-induction-of-oxidative-stress-in-vitro-in-brain-of-adolescent-rats
#14
Janaína Camacho da Silva, Alexandre Umpierrez Amaral, Cristiane Cecatto, Alessandro Wajner, Kálita Dos Santos Godoy, Rafael Teixeira Ribeiro, Aline de Mello Gonçalves, Ângela Zanatta, Mateus Struecker da Rosa, Samanta Oliveira Loureiro, Carmen Regla Vargas, Guilhian Leipnitz, Diogo Onofre Gomes de Souza, Moacir Wajner
Tissue accumulation of α-ketoadipic (KAA) and α-aminoadipic (AAA) acids is the biochemical hallmark of α-ketoadipic aciduria. This inborn error of metabolism is currently considered a biochemical phenotype with uncertain clinical significance. Considering that KAA and AAA are structurally similar to α-ketoglutarate and glutamate, respectively, we investigated the in vitro effects of these compounds on glutamatergic neurotransmission in the brain of adolescent rats. Bioenergetics and redox homeostasis were also investigated because they represent fundamental systems for brain development and functioning...
April 20, 2017: Neurotoxicity Research
https://www.readbyqxmd.com/read/28429259/early-morphological-and-functional-changes-in-the-gabaergic-system-of-hippocampus-in-the-rat-lithium-pilocarpine-model-of-epilepsy
#15
V B Karyakin, D S Vasil'ev, I A Zhuravin, A V Zaitsev, L G Magazanik
We studied early alterations in the GABAergic system of the rat hippocampus in the lithium-pilocarpine model of epilepsy. Twenty-four hours after the pilocarpine treatment, a decrease in the number of calretinin-positive interneurons was observed in the CA1 field of the hippocampus, whereas the number of parvalbumin-positive interneurons remained unchanged. The decreased levels of the GABA-synthesizing enzyme glutamic acid decarboxylase (GAD67) and the membrane GABA transporter GAT1 were revealed using Western blot analysis...
January 2017: Doklady Biological Sciences: Proceedings of the Academy of Sciences of the USSR, Biological Sciences Sections
https://www.readbyqxmd.com/read/28428755/pharmacological-analysis-of-the-anti-epileptic-mechanisms-of-fenfluramine-in-scn1a-mutant-zebrafish
#16
Jo Sourbron, Ilse Smolders, Peter de Witte, Lieven Lagae
Dravet syndrome (DS) is a genetic encephalopathy that is characterized by severe seizures and prominent co-morbidities (e.g., physical, intellectual disabilities). More than 85% of the DS patients carry an SCN1A mutation (sodium channel, voltage gated, type I alpha subunit). Although numerous anti-epileptic drugs have entered the market since 1990, these drugs often fail to adequately control seizures in DS patients. Nonetheless, current clinical data shows significant seizure reduction in DS patients treated with the serotonergic (5-hydroxytryptamine, 5-HT) drug fenfluramine (FA)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28428223/glutamatergic-mechanisms-involved-in-bladder-overactivity-and-pudendal-neuromodulation-in-cats
#17
Jamie Uy, Michelle Yu, Xuewen Jiang, Cameron Jones, Bing Shen, Jicheng Wang, James R Roppolo, William C de Groat, Changfeng Tai
The involvement of ionotropic glutamate receptors in bladder overactivity and pudendal neuromodulation was determined in α-chloralose anesthetized cats by intravenously administering MK801 (a NMDA receptor antagonist) or CP465022 (an AMPA receptor antagonist). Infusion of 0.5% acetic acid (AA) into the bladder produced bladder overactivity. In the first group of 5 cats, bladder capacity was significantly (p<0.05) reduced to 55.3±10.0% of saline control by AA irritation. Pudendal nerve stimulation (PNS) significantly (p<0...
April 20, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/28426698/extensive-alterations-of-blood-metabolites-in-pediatric-cerebral-malaria
#18
Sanchit Gupta, Karl Seydel, Miguel A Miranda-Roman, Catherine M Feintuch, Alex Saidi, Ryung S Kim, Gretchen L Birbeck, Terrie Taylor, Johanna P Daily
Cerebral malaria (CM) presents as an encephalopathy and is due to infection with Plasmodium falciparum. Patients are comatose, often with fever, recurrent seizures and this condition is associated with a high mortality rate. The etiology of the coma and seizures are poorly understood. Circulating small molecules and lipids have bioactive functions and alterations in their concentrations have been implicated in seizure disorders and other forms of encephalopathy. We carried out a comprehensive analysis of blood metabolites during CM to explore a biochemical basis of this encephalopathy...
2017: PloS One
https://www.readbyqxmd.com/read/28426073/ameliorative-effects-of-pepsin-digested-chicken-liver-hydrolysates-on-development-of-alcoholic-fatty-livers-in-mice
#19
Yi-Ling Lin, Szu-Yun Tai, Jr-Wei Chen, Chung-Hsi Chou, Shih-Guei Fu, Yi-Chen Chen
With developments in economics and increasing work loads, alcohol abuse becomes more and more severe, leading to occurrences of alcoholic liver disease (ALD). Pepsin-digested chicken liver hydrolysates (CLHs) contain high amounts of glutamic acid, leucine, lysine, and alanine while the contents of taurine, anserine, and carnosine are also elevated after pepsin hydrolyzation. The objectives of this study were to evaluate the protective effects of CLHs against chronic alcohol consumption. The results indicated that the enlarged (p < 0...
April 20, 2017: Food & Function
https://www.readbyqxmd.com/read/28424047/deciphering-mechanisms-underlying-the-genetic-variation-of-general-production-and-liver-quality-traits-in-the-overfed-mule-duck-by-pqtl-analyses
#20
Yoannah François, Alain Vignal, Caroline Molette, Nathalie Marty-Gasset, Stéphane Davail, Laurence Liaubet, Christel Marie-Etancelin
BACKGROUND: The aim of this study was to analyse the mechanisms that underlie phenotypic quantitative trait loci (QTL) in overfed mule ducks by identifying co-localized proteomic QTL (pQTL). The QTL design consisted of three families of common ducks that were progeny-tested by using 294 male mule ducks. This population of common ducks was genotyped using a genetic map that included 334 genetic markers located across 28 APL chromosomes (APL for Anas platyrhynchos). Mule ducks were phenotyped for 49 traits related to growth, metabolism, overfeeding ability and meat and fatty liver quality, and 326 soluble fatty liver proteins were quantified...
April 19, 2017: Genetics, Selection, Evolution: GSE
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