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https://www.readbyqxmd.com/read/29471227/the-impact-of-acute-and-short-term-methamphetamine-abstinence-on-brain-metabolites-a-proton-magnetic-resonance-spectroscopy-chemical-shift-imaging-study
#1
Antoinette Burger, Samantha J Brooks, Dan J Stein, Fleur M Howells
BACKGROUND: Abuse of methamphetamine (MA) is a global health concern. Previous1 H-MRS studies have found that, with methamphetamine abstinence (MAA), there are changes in n-acetyl-aspartate (NAA/Cr), myo-inositol (mI/Cr), choline (Cho/Cr and Cho/NAA), and glutamate with glutamine (Glx) metabolites. Limited studies have investigated the effect of acute MAA, and acute-to-short-term MAA on brain metabolites. METHODS: Adults with chronic MA dependence (n = 31) and healthy controls (n = 22) were recruited...
February 19, 2018: Drug and Alcohol Dependence
https://www.readbyqxmd.com/read/29469028/effects-of-short-term-dietary-restriction-and-glutamine-supplementation-in-vitro-on-the-modulation-of-inflammatory-properties
#2
Dalila C de Oliveira, Ed Wilson Santos, Amanda Nogueira-Pedro, José Guilherme Xavier, Primavera Borelli, Ricardo Ambrósio Fock
OBJECTIVE: Dietary restriction (DR) is a nutritional intervention that exerts profound effects on biochemical and immunologic parameters, modulating some inflammatory properties. Glutamine (GLN) is a conditionally essential amino acid that can modulate inflammatory properties. However, there is a lack of data evaluating the effects of DR and GLN supplementation, especially in relation to inflammatory cytokine production and the expression of transcription factors such as nuclear factor (NF)-κB...
December 11, 2017: Nutrition
https://www.readbyqxmd.com/read/29468182/-gls-loss-of-function-causes-autosomal-recessive-spastic-ataxia-and-optic-atrophy
#3
David S Lynch, Viorica Chelban, Jana Vandrovcova, Alan Pittman, Nicholas W Wood, Henry Houlden
We describe a consanguineous family in which two brothers were affected by childhood onset spastic ataxia with optic atrophy and loss of motor and language skills. Through a combination of homozygosity mapping and whole-genome sequencing, we identified a homozygous copy number variant in GLS as the cause. The duplication leads to complete knockout of GLS expression. GLS encodes the brain- and kidney-specific enzyme glutaminase, which hydrolyzes glutamine for the production of glutamate, the most abundant central nervous system neurotransmitter...
February 2018: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29468164/glutamine-hydrolysis-by-imidazole-glycerol-phosphate-synthase-displays-temperature-dependent-allosteric-activation
#4
George P Lisi, Allen A Currier, J Patrick Loria
The enzyme imidazole glycerol phosphate synthase (IGPS) is a model for studies of long-range allosteric regulation in enzymes. Binding of the allosteric effector ligand N'-[5'-phosphoribulosyl)formimino]-5-aminoimidazole-4-carboxamide-ribonucleotide (PRFAR) stimulates millisecond (ms) timescale motions in IGPS that enhance its catalytic function. We studied the effect of temperature on these critical conformational motions and the catalytic mechanism of IGPS from the hyperthermophile Thermatoga maritima in an effort to understand temperature-dependent allostery...
2018: Frontiers in Molecular Biosciences
https://www.readbyqxmd.com/read/29467657/effects-of-sodium-and-amino-acid-substrate-availability-upon-the-expression-and-stability-of-the-snat2-slc38a2-amino-acid-transporter
#5
Thorsten M Hoffmann, Emma Cwiklinski, Dinesh S Shah, Clare Stretton, Russell Hyde, Peter M Taylor, Harinder S Hundal
The SNAT2 (SLC38A2) System A amino acid transporter mediates Na+ -coupled cellular uptake of small neutral α-amino acids (AAs) and is extensively regulated in response to humoral and nutritional cues. Understanding the basis of such regulation is important given that AA uptake via SNAT2 has been linked to activation of mTORC1; a major controller of many important cellular processes including, for example, mRNA translation, lipid synthesis, and autophagy and whose dysregulation has been implicated in the development of cancer and conditions such as obesity and type 2 diabetes...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29466723/small-molecule-screen-identifies-de-novo-nucleotide-synthesis-as-a-vulnerability-of-cells-lacking-sirt3
#6
Karina N Gonzalez Herrera, Elma Zaganjor, Yoshinori Ishikawa, Jessica B Spinelli, Haejin Yoon, Jia-Ren Lin, F Kyle Satterstrom, Alison Ringel, Stacy Mulei, Amanda Souza, Joshua M Gorham, Craig C Benson, Jonathan G Seidman, Peter K Sorger, Clary B Clish, Marcia C Haigis
Sirtuin 3 (SIRT3) is a NAD+ -dependent deacetylase downregulated in aging and age-associated diseases such as cancer and neurodegeneration and in high-fat diet (HFD)-induced metabolic disorders. Here, we performed a small-molecule screen and identified an unexpected metabolic vulnerability associated with SIRT3 loss. Azaserine, a glutamine analog, was the top compound that inhibited growth and proliferation of cells lacking SIRT3. Using stable isotope tracing of glutamine, we observed its increased incorporation into de novo nucleotide synthesis in SIRT3 knockout (KO) cells...
February 20, 2018: Cell Reports
https://www.readbyqxmd.com/read/29463741/transcriptional-factor-icer-promotes-glutaminolysis-and-the-generation-of-th17-cells
#7
Michihito Kono, Nobuya Yoshida, Kayaho Maeda, George C Tsokos
Glutaminolysis is a well-known source of energy for effector T cells but its contribution to each T cell subset and the mechanisms which are responsible for the control of involved metabolic enzymes are not fully understood. We report that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on glutaminolysis and the up-regulation of glutaminase 1 (Gls1), the first enzyme in the glutaminolysis pathway. Both pharmacological and siRNA-based selective inhibition of Gls1 reduced in vitro Th17 differentiation and reduced the CD3/TCR-mediated increase of the mammalian target of rapamycin complex 1 activity...
February 20, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29463564/glutaminolysis-is-a-metabolic-dependency-in-flt3-itd-acute-myeloid-leukemia-unmasked-by-flt3-tyrosine-kinase-inhibition
#8
Paolo Gallipoli, George Giotopoulos, Konstantinos Tzelepis, Ana S H Costa, Shabana Vohra, Paula Medina-Perez, Faisal Basheer, Ludovica Marando, Lorena Di Lisio, Joao M L Dias, Haiyang Yun, Daniel Sasca, Sarah J Horton, George Vassiliou, Christian Frezza, Brian J P Huntly
FLT3 internal tandem duplication (FLT3ITD ) are common mutations in acute myeloid leukemia (AML) associated with poor patient prognosis. Although new generation FLT3 tyrosine kinase inhibitors (TKI) have shown promising results, the outcome of FLT3ITD AML patients remains poor and demands the identification of novel, specific and validated therapeutic targets for this highly aggressive AML subtype. Utilizing an unbiased genome-wide CRISPR/Cas9 screen, we identify GLS, the first enzyme in glutamine metabolism, as synthetically lethal with FLT3-TKI treatment...
February 20, 2018: Blood
https://www.readbyqxmd.com/read/29463319/performance-of-arma-chinensis-reared-on-an-artificial-diet-formulated-using-transcriptomic-methods
#9
D Y Zou, T A Coudron, L S Zhang, X S Gu, W H Xu, X L Liu, H H Wu
An artificial diet formulated for continuous rearing of the predator Arma chinensis was inferior to natural prey when evaluated using life history parameters. A transcriptome analysis identified differentially expressed genes in diet-fed and prey-fed A. chinensis that were suggestive of molecular mechanisms underlying the nutritive impact of the artificial diet. Changes in the diet formulation were made based on the transcriptome analysis and tested using life history parameters. The quantity of pig liver, chicken egg, tuna fish, biotin, nicotinamide, vitamin B6, thiamine, riboflavin, vitamin C, L-glutamine, and sucrose was reduced, and wheat germ oil, calcium pantothenate and folic acid were increased...
February 21, 2018: Bulletin of Entomological Research
https://www.readbyqxmd.com/read/29463059/glutamine-synthetase-localization-dictates-outcome
#10
REVIEW
Alessandra Castegna, Alessio Menga
Glutamine synthetase (GS) is the adenosine triphosphate (ATP)-dependent enzyme that catalyses the synthesis of glutamine by condensing ammonium to glutamate. In the circulatory system, glutamine carries ammonia from muscle and brain to the kidney and liver. In brain reduction of GS activity has been suggested as a mechanism mediating neurotoxicity in neurodegenerative disorders. In cancer, the delicate balance between glutamine synthesis and catabolism is a critical event. In vitro evidence, confirmed in vivo in some cases, suggests that reduced GS activity in cancer cells associates with a more invasive and aggressive phenotype...
February 19, 2018: Genes
https://www.readbyqxmd.com/read/29462792/-arabidopsis-thaliana-gh3-15-acyl-acid-amido-synthetase-has-a-highly-specific-substrate-preference-for-the-auxin-precursor-indole-3-butyric-acid
#11
Ashley M Sherp, Corey S Westfall, Sophie Alvarez, Joseph M Jez
Various phytohormones control plant growth and development and mediate biotic and abiotic stress responses. Gretchen Hagen 3 (GH3) acyl acid amido synthetases are plant enzymes that typically conjugate amino acids to indole-3-acetic acid (IAA) or jasmonic acid (JA) to inactivate or activate these phytohormones, respectively; however, the physiological and biological roles of many of these enzymes remain unclear. Using a biochemical approach, we found that the Arabidopsis thaliana GH3.15 (AtGH3.15) preferentially uses the acyl acid and auxin indole-3-butyric acid (IBA) and the amino acid glutamine as substrates...
February 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29462606/limb-remote-ischemic-post-conditioning-mitigates-brain-recovery-in-a-mouse-model-of-ischemic-stroke-by-regulating-reactive-astrocytic-plasticity
#12
Xue Cheng, Haiping Zhao, Feng Yan, Zhen Tao, Rongliang Wang, Ziping Han, Guangwen Li, Yumin Luo, Xunming Ji
Maladaptive alterations of astrocytic plasticity may cause brain edema in the acute stage of stroke and glial scar formation in the recovery stage. The present study was designed to investigate the potential regulation of limb remote ischemic post-conditioning (RIPC) on astrocytic plasticity in experimental cerebral ischemia-reperfusion injury. Cerebral ischemia was induced by transient middle cerebral artery occlusion (tMCAO) for 1 h in C57BL/6 mice, who were treated with RIPC immediately after reperfusion...
February 17, 2018: Brain Research
https://www.readbyqxmd.com/read/29460801/effects-of-glucocorticoids-on-serum-amino-acid-levels-during-cardiac-surgery-in-children
#13
Annelies van Zwol, Neelke B C Oosterloo, Cartijn T de Betue, Ad Bogers, Inge I de Liefde, Nicolaas E P Deutz, Koen F M Joosten
BACKGROUND AND AIMS: Children undergoing cardiac surgery with cardio pulmonary bypass often receive glucocorticoids to reduce the systemic inflammatory response. Glucocorticoids stimulate protein breakdown and increase amino acid availability. We studied whether glucocorticoid treatment influences the availability of amino acids, specifically those involved in the nitric oxide pathway. METHODS: We prospectively studied 49 children with congenital heart disease undergoing cardiac surgery...
February 2018: Clinical Nutrition ESPEN
https://www.readbyqxmd.com/read/29459886/dna-damage-repair-and-cancer-metabolism
#14
REVIEW
Marc-Olivier Turgeon, Nicholas J S Perry, George Poulogiannis
Although there has been a renewed interest in the field of cancer metabolism in the last decade, the link between metabolism and DNA damage/DNA repair in cancer has yet to be appreciably explored. In this review, we examine the evidence connecting DNA damage and repair mechanisms with cell metabolism through three principal links. (1) Regulation of methyl- and acetyl-group donors through different metabolic pathways can impact DNA folding and remodeling, an essential part of accurate double strand break repair...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29459673/specific-recognition-of-arginine-methylated-histone-tails-by-jmjd5-and-jmjd7
#15
Haolin Liu, Chao Wang, Schuyler Lee, Fangkun Ning, Yang Wang, Qianqian Zhang, Zhongzhou Chen, Jianye Zang, Jay Nix, Shaodong Dai, Philippa Marrack, James Hagman, John Kappler, Gongyi Zhang
We have reported that JMJD5 and JMJD7 (JMJD5/7) are responsible for the clipping of arginine methylated histone tails to generate "tailless nucleosomes", which could release the pausing RNA polymerase II (Pol II) into productive transcription elongation. JMJD5/7 function as endopeptidases that cleave histone tails specifically adjacent to methylated arginine residues and continue to degrade N-terminal residues of histones via their aminopeptidase activity. Here, we report structural and biochemical studies on JMJD5/7 to understand the basis of substrate recognition and catalysis mechanism by this JmjC subfamily...
February 19, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29459179/nmr-analysis-of-substrate-binding-to-a-two-domain-chitinase-comparison-between-soluble-and-insoluble-chitins
#16
Tomoya Takashima, Takayuki Ohnuma, Tamo Fukamizo
CJP-4 is a two-domain chitinase from Japanese cedar (Cryptomeria japonica) pollen, consisting of an N-terminal CBM18 domain and a GH19 catalytic domain. The substrate binding to an inactive mutant protein of full-length CJP-4, in which the catalytic acid Glu108 was mutated to glutamine, CJP-4(E108Q), was analyzed by NMR spectroscopy. Based on the chemical shift perturbations of1 H-15 N HSQC signals of Gly26 (CBM18 domain) and Trp185 (GH19 domain), the association constants for individual domains of CJP-4(E108Q) toward soluble chitin hexamer (GlcNAc)6 were determined to be 2300 and 3500 M-1 , respectively...
February 8, 2018: Carbohydrate Research
https://www.readbyqxmd.com/read/29457680/chronic-lead-exposure-enhances-the-sympathoexcitatory-response-associated-with-p2x4-receptor-in-rat-stellate-ganglia
#17
Gaochun Zhu, Zhenying Chen, Bo Dai, Chaoran Zheng, Huaide Jiang, Yurong Xu, Xuan Sheng, Jingjing Guo, Yu Dan, Shangdong Liang, Guilin Li
Chronic lead exposure causes peripheral sympathetic nerve stimulation, including increased blood pressure and heart rate. Purinergic receptors are involved in the sympathoexcitatory response induced by myocardial ischemia injury. However, whether P2X4 receptor participates in sympathoexcitatory response induced by chronic lead exposure and the possible mechanisms are still unknown. The aim of this study was to explore the change of the sympathoexcitatory response induced by chronic lead exposure via the P2X4 receptor in the stellate ganglion (SG)...
February 19, 2018: Environmental Toxicology
https://www.readbyqxmd.com/read/29455869/overexpression-of-slc1a5-in-lymph-node-metastases-outperforms-assessment-in-the-primary-as-a-negative-prognosticator-in-non-small-cell-lung-cancer
#18
Agnes Csanadi, Annika Oser, Konrad Aumann, Vera Gumpp, Justyna Rawluk, Ursula Nestle, Claudia Kayser, Sebastian Wiesemann, Martin Werner, Gian Kayser
Despite recent advances in therapeutic options, lung cancer is the leading cause of death among malignant diseases worldwide. Glutamine-dependence is an established attribute in cancer tissue with emerging importance as a diagnostic and therapeutic target. We analysed the expression of SLC1a5, a major glutamine transporter, in the primary tumour and corresponding nodal metastasis of non-small cell lung cancer (NSCLC) to investigate its biological impact. Expression of SLC1a5 was analysed by immunohistochemistry in 259 NSCLC and in 142 nodal metastases and correlated with clinicopathological parameters including overall survival...
February 15, 2018: Pathology
https://www.readbyqxmd.com/read/29455543/effect-of-leucine-on-nf-%C3%AE%C2%BAb-pathway-in-liver-regeneration-after-partial-hepatectomy-in-rats-as-determined-by-miniarray-analysis
#19
E Ceyhan, M Canbek, M Uyanoglu, A Ozen, B Durmus Ozen, B Berber, A Ozmen Yaylaci, L Resulzade
BACKGROUND: Although some amino acids are recognized to have favorable effects on the liver regeneration after partial hepatectomy (PH), molecular mechanisms underlying these effects are barely known. OBJECTIVE: Our study was aimed to investigate the effects of valine, glutamine, and leucine amino acids on PH-induced NF-κB signal pathway. The research team studied Leucine in a rat model in vivo. The study took place in the medical and surgical experimental research center at the Eskisehir Osmangazi University in Eskisehir, Turkey...
2018: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/29455251/establishing-and-characterizing-lacrispheres-from-human-lacrimal-gland-for-potential-clinical-application
#20
Shubha Tiwari, Rohini M Nair, Praseeda Vamadevan, Mohammad Javed Ali, Milind N Naik, Santosh G Honavar, Geeta K Vemuganti
PURPOSE: Lacrimal gland (LG) dysfunction leading to dry eye syndrome (DES) is an important cause of ocular morbidity. One of the potential and promising long-term management therapies for restoration of LG function could be transplantation of autologous ex vivo expanded stem cells. The present study was aimed at exploring the 2D and 3D cultures of human LG, identifying inherent stem cells and evaluating their secretory potential. METHODS: Fresh human lacrimal gland (HuLG) (n = 5) from patients undergoing therapeutic exenteration was harvested after ethical approval and informed consent...
February 17, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
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