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https://www.readbyqxmd.com/read/28342810/expression-and-putative-role-of-mitochondrial-transport-proteins-in-cancer
#1
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
#2
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/28339983/acr11-is-an-activator-of-plastid-type-glutamine-synthetase-gs2-in-arabidopsis-thaliana
#3
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
#4
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
#5
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/28333211/glutathione-affects-the-transport-activity-of-rhizobium-leguminosarum-3841-and-is-essential-for-efficient-nodulation
#6
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/28331060/proximal-tubule-glutamine-synthetase-expression-is-necessary-for-the-normal-response-to-dietary-protein-restriction
#7
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/28330175/exploration-of-the-binding-modes-of-l-asparaginase-complexed-with-its-amino-acid-substrates-by-molecular-docking-dynamics-and-simulation
#8
Erva Rajeswara Reddy, Rajulapati Satish Babu, Potla Durthi Chandrasai, Pola Madhuri
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-glutamine (L-Gln) deamination plays crucial role in ALL treatment. Role of Erwinaze(®) (L-asparaginase from Erwinia chrysanthemi) in regulation of L-Asn and L-Gln has been confirmed by the experimental studies. Therapeutic research against ALL remained elusive with the lack of structural information on Erwinaze(®) enzyme. In this present study, homology model of the Erwinaze(®) was developed using MODELLER and the same was validated by various quality indexing tools...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28330072/molecular-dynamic-simulations-of-escherichia-coli-l-asparaginase-to-illuminate-its-role-in-deamination-of-asparagine-and-glutamine-residues
#9
Rajeswara Reddy Erva, Satish Babu Rajulapati, Chandrasai Potla Durthi, Mayuri Bhatia, Madhuri Pola
Acute lymphocytic leukemia (ALL) is an outrageous disease worldwide. L-Asparagine (L-Asn) and L-Glutamine (L-Gln) deamination play a crucial role in ALL treatment. Role of Elspar(®) (L-asparaginase from Escherichia coli) in regulation of L-Asn and L-Gln has been confirmed by the other researchers through experimental studies. Therapeutic research against ALL remained elusive with the lack of information on molecular interactions of Elspar(®) with amino acid substrates. In the present study, using different docking tools binding cavities, key residues in binding and ligand binding mechanisms were identified...
June 2016: 3 Biotech
https://www.readbyqxmd.com/read/28327670/global-identification-and-analysis-of-isozyme-specific-possible-substrates-crosslinked-by-transglutaminases-using-substrate-peptides-in-mouse-liver-fibrosis
#10
Hideki Tatsukawa, Yuji Tani, Risa Otsu, Haruka Nakagawa, Kiyotaka Hitomi
The transglutaminase (TG) family comprises eight isozymes that form the isopeptide bonds between glutamine and lysine residues and contribute to the fibrotic diseases via crosslinking-mediated stabilization of ECM and the activation of TGF-β in several tissues. However, despite a growing body of evidence implicating TG2 as a key enzyme in fibrosis, the causative role of TG2 and the involvement of the other isozymes have not yet been fully elucidated. Therefore, here we clarified the distributions of TG isozymes and their in situ activities and identified the isozyme-specific possible substrates for both TG1 and TG2 using their substrate peptides in mouse fibrotic liver...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28320958/p97-vcp-promotes-degradation-of-crbn-substrate-glutamine-synthetase-and-neosubstrates
#11
Thang Van Nguyen, Jing Li, Chin-Chun Jean Lu, Jennifer L Mamrosh, Gang Lu, Brian E Cathers, Raymond J Deshaies
Glutamine synthetase (GS) plays an essential role in metabolism by catalyzing the synthesis of glutamine from glutamate and ammonia. Our recent study showed that CRBN, a direct protein target for the teratogenic and antitumor activities of immunomodulatory drugs such as thalidomide, lenalidomide, and pomalidomide, recognizes an acetyl degron of GS, resulting in ubiquitylation and degradation of GS in response to glutamine. Here, we report that valosin-containing protein (VCP)/p97 promotes the degradation of ubiquitylated GS, resulting in its accumulation in cells with compromised p97 function...
March 20, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28315295/proton-nmr-metabolic-profiling-of-csf-reveals-distinct-differentiation-of-meningitis-from-negative-controls
#12
Tanushri Chatterji, Suruchi Singh, Manodeep Sen, Ajai Kumar Singh, Gaurav Raj Agarwal, Deepak Kumar Singh, Janmejai Kumar Srivastava, Alka Singh, Rajendra Nath Srivastava, Raja Roy
BACKGROUND: Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). METHODS: The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA)...
March 14, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28314989/inhibition-of-got1-sensitizes-colorectal-cancer-cells-to-5-fluorouracil
#13
Chengyu Hong, Jian Zheng, Xiaoling Li
PURPOSE: Almost all colorectal cancer (CRC) cell lines are known to overexpress aspartate aminotransferase (GOT1), which potentially regulates the intracellular levels of reactive oxygen species (ROS) via the production of NADPH, and supports tumor growth. In our study, the role of GOT1 in the anticancer efficacy of 5-fluorouracil (5-FU) was examined. METHODS: HCT116, SW480, and HT-29 cells were transfected with lentiviral vectors expressing short hairpin RNA (shRNA) against GOT1...
March 17, 2017: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/28314820/amyloid-precursor-protein-in-drosophila-glia-regulates-sleep-and-genes-involved-in-glutamate-recycling
#14
Abud Jose Farca Luna, Magali Perier, Laurent Seugnet
The Amyloid Precursor Protein (App) plays a crucial role in Alzheimer disease (AD) via the production and deposition of toxic β-amyloid peptides. App is heavily expressed in neurons where the vast majority of studies investigating its function have been carried out, while almost nothing is known about its function in glia, where it is also expressed, and can potentially participate in the regulation of neuronal physiology. In this report, we investigated whether Appl, the Drosophila homolog of App, could influence sleep-wake regulation when its function is manipulated in glial cells...
March 17, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28306503/phase-separation-of-c9orf72-dipeptide-repeats-perturbs-stress-granule-dynamics
#15
Steven Boeynaems, Elke Bogaert, Denes Kovacs, Albert Konijnenberg, Evy Timmerman, Alex Volkov, Mainak Guharoy, Mathias De Decker, Tom Jaspers, Veronica H Ryan, Abigail M Janke, Pieter Baatsen, Thomas Vercruysse, Regina-Maria Kolaitis, Dirk Daelemans, J Paul Taylor, Nancy Kedersha, Paul Anderson, Francis Impens, Frank Sobott, Joost Schymkowitz, Frederic Rousseau, Nicolas L Fawzi, Wim Robberecht, Philip Van Damme, Peter Tompa, Ludo Van Den Bosch
Liquid-liquid phase separation (LLPS) of RNA-binding proteins plays an important role in the formation of multiple membrane-less organelles involved in RNA metabolism, including stress granules. Defects in stress granule homeostasis constitute a cornerstone of ALS/FTLD pathogenesis. Polar residues (tyrosine and glutamine) have been previously demonstrated to be critical for phase separation of ALS-linked stress granule proteins. We now identify an active role for arginine-rich domains in these phase separations...
March 16, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28301735/glutaminolysis-a-hallmark-of-cancer-metabolism
#16
Lifeng Yang, Sriram Venneti, Deepak Nagrath
Glutamine is the most abundant circulating amino acid in blood and muscle and is critical for many fundamental cell functions in cancer cells, including synthesis of metabolites that maintain mitochondrial metabolism; generation of antioxidants to remove reactive oxygen species; synthesis of nonessential amino acids (NEAAs), purines and pyrimidines, and fatty acids for cellular replication; and activation of cell signaling. In light of the pleiotropic role of glutamine in cancer cells, a comprehensive understanding of glutamine metabolism is essential for the development of metabolic therapeutic strategies for targeting cancer cells...
March 8, 2017: Annual Review of Biomedical Engineering
https://www.readbyqxmd.com/read/28296572/srna154-a-newly-identified-regulator-of-nitrogen-fixation-in-methanosarcina%C3%A2-mazei-strain-g%C3%A3-1
#17
Daniela Prasse, Konrad U Förstner, Dominik Jäger, Rolf Backofen, Ruth A Schmitz
Trans-encoded sRNA154 is exclusively expressed under nitrogen (N)-deficiency in Methanosarcina mazei strain Gö1. The sRNA154 deletion strain showed a significant decrease in growth under N-limitation, pointing towards a regulatory role of sRNA154 in N-metabolism. Aiming to elucidate its regulatory function we characterized sRNA154 by means of biochemical and genetic approaches. 24 homologs of sRNA154 were identified in recently reported draft genomes of Methanosarcina strains, demonstrating high conservation in sequence and predicted secondary structure with two highly conserved single stranded loops...
March 15, 2017: RNA Biology
https://www.readbyqxmd.com/read/28296004/nitrogen-modulation-of-medicago-truncatula-resistance-to-aphanomyces-euteiches-depends-on-plant-genotype
#18
Elise Thalineau, Carine Fournier, Antoine Gravot, David Wendehenne, Sylvain Jeandroz, Hoai-Nam Truong
Nitrogen (N) availability can impact plant resistance to pathogens by regulating plant immunity. To better understand the links between N nutrition and plant defence, we analysed the impact of N availability on Medicago truncatula resistance to the root pathogen Aphanomyces euteiches. This oomycete is considered as the most limiting factor for legume production. Ten plant genotypes were tested in vitro for their resistance to A. euteiches in either complete or N-deficient medium. N-deficiency led to enhanced or reduced susceptibility depending on plant genotype...
March 15, 2017: Molecular Plant Pathology
https://www.readbyqxmd.com/read/28295918/the-intrinsically-disordered-inhibitor-of-glutamine-synthetase-is-a-functional-protein-with-random-coil-like-pka-values
#19
Concetta Cozza, José L Neira, Francisco J Florencio, M Isabel Muro-Pastor, Bruno Rizzuti
The sequential action of glutamine synthetase (GS) and glutamate synthase (GOGAT) in cyanobacteria allows the incorporation of ammonium into carbon skeletons. In the cyanobacterium Synechocystis sp. PCC 6803, the activity of GS is modulated by the interaction with proteins, which include a 65-residue-long intrinsically disordered protein (IDP), the inactivating factor IF7. This interaction is regulated by the presence of charged residues in both IF7 and GS. In order to understand how charged amino acids can affect the binding of an IDP with its target, and to provide clues on electrostatic interactions in disordered states of proteins, we measured the pKa values of all IF7 acidic groups (Glu32, Glu36, Glu38, Asp40, Asp58, and Ser65, the backbone C-terminus) at 100 mM NaCl concentration, by using NMR spectroscopy...
March 15, 2017: Protein Science: a Publication of the Protein Society
https://www.readbyqxmd.com/read/28295144/androgen-receptor-polyglutamine-repeat-length-ar-cagn-modulates-the-effect-of-testosterone-on-androgen-associated-somatic-traits-in-filipino-young-adult-men
#20
Calen P Ryan, Alexander V Georgiev, Thomas W McDade, Lee T Gettler, Dan T A Eisenberg, Margarita Rzhetskaya, Sonny S Agustin, M Geoffrey Hayes, Christopher W Kuzawa
OBJECTIVES: The androgen receptor (AR) mediates expression of androgen-associated somatic traits such as muscle mass and strength. Within the human AR is a highly variable glutamine short-tandem repeat (AR-CAGn), and CAG repeat number has been inversely correlated to AR transcriptional activity in vitro. However, evidence for an attenuating effect of long AR-CAGn on androgen-associated somatic traits has been inconsistent in human populations. One possible explanation for this lack of consistency is that the effect of AR-CAGn on AR bioactivity in target tissues likely varies in relation to circulating androgen levels...
March 14, 2017: American Journal of Physical Anthropology
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