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https://www.readbyqxmd.com/read/29337138/let-7-suppresses-b-cell-activation-through-restricting-the-availability-of-necessary-nutrients
#1
Shuai Jiang, Wei Yan, Shizhen Emily Wang, David Baltimore
The control of uptake and utilization of necessary extracellular nutrients-glucose and glutamine-is an important aspect of B cell activation. Let-7 is a family of microRNAs known to be involved in metabolic control. Here, we employed several engineered mouse models, including B cell-specific overexpression of Lin28a or the let-7a-1/let-7d/let-7f-1 cluster (let-7adf) and knockout of individual let-7 clusters to show that let-7adf specifically inhibits T cell-independent (TI) antigen-induced immunoglobulin (Ig)M antibody production...
January 10, 2018: Cell Metabolism
https://www.readbyqxmd.com/read/29335634/the-pii-signaling-protein-from-red-algae-represents-an-evolutionary-link-between-cyanobacterial-and-chloroplastida-pii-proteins
#2
Tatyana Lapina, Khaled A Selim, Karl Forchhammer, Elena Ermilova
PII superfamily consists of widespread signal transduction proteins found in all domains of life. Whereas they are well-studied in Archaea, Bacteria and Chloroplastida, no PII homolog has been analyzed in Rhodophyta (red algae), where PII is encoded by a chloroplast localized glnB gene. Here, we characterized relevant sensory properties of PII from the red alga Porphyra purpurea (PpPII) in comparison to PII proteins from different phyla of oxygenic phototrophs (cyanobacteria, Chlamydomonas and Physcomitrella) to assess evolutionary conservation versus adaptive properties...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29331336/udp-sugar-accumulation-drives-hyaluronan-synthesis-in-breast-cancer
#3
Sanna Oikari, Tiia Kettunen, Satu Tiainen, Jukka Häyrinen, Amro Masarwah, Mazen Sudah, Anna Sutela, Ritva Vanninen, Markku Tammi, Päivi Auvinen
Increased uptake of glucose, a general hallmark of malignant tumors, leads to an accumulation of intermediate metabolites of glycolysis. We investigated whether the high supply of these intermediates promotes their flow into UDP-sugars, and consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human breast cancer biopsies, the levels of enzymes contributing to their synthesis, and their association with the hyaluronan accumulation in the tumor...
January 10, 2018: Matrix Biology: Journal of the International Society for Matrix Biology
https://www.readbyqxmd.com/read/29326164/the-glutamine-transporter-asct2-slc1a5-promotes-tumor-growth-independently-of-the-amino-acid-transporter-lat1-slc7a5
#4
Yann Cormerais, Pierre André Massard, Milica Vucetic, Sandy Giuliano, Eric Tambutté, Jerome Durivault, Valérie Vial, Hitoshi Endou, Michael F Wempe, Scott K Parks, Jacques Pouyssegur
The transporters for glutamine and essential amino acids (EAA), ASCT2 (solute carrier family 1 member 5, SLC1A5), and LAT1 (solute carrier family 7 member 5, SLC7A5), respectively are overexpressed in aggressive cancers and have been identified as cancer-promoting targets. Moreover, previous work has suggested that glutamine influx via ASCT2 triggers EAA entry via the LAT1 exchanger, thus activating mechanistic target of rapamycin complex 1 (mTORC1) and stimulating growth. Here, to further investigate whether these two transporters are functionally coupled, we compared the respective knockout (KO) of either LAT1 or ASCT2 in colon (LS174T) and lung (A549) adenocarcinoma cell lines...
January 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29324050/the-roles-of-adjuvant-supplements-in-colorectal-cancer-patients-on-chemotherapy-reaping-benefits-from-metabolic-crosstalk
#5
Babak Golkhalkhali, Audra Shaleena Paliany, Kin Fah Chin, Retnagowri Rajandram
The prevalence of colorectal cancer (CRC) is on a steady rise over the years, with the World Health Organization (WHO) reporting CRC as the fourth leading cause of cancer-related death worldwide. While treatment modalities may differ in accordance to the staging and severity of the disease itself, chemotherapy is almost unavoidable in most cases. Though effective in its mode of action, chemotherapy is commonly associated with undesirable side effects that negatively affects the patient in terms of quality of life, and in some cases may actually interfere with their treatment regimens, thus escalating to poor prognosis...
January 11, 2018: Nutrition and Cancer
https://www.readbyqxmd.com/read/29320490/the-glutamine-synthetase-of-trypanosoma-cruzi-is-required-for-its-resistance-to-ammonium-accumulation-and-evasion-of-the-parasitophorous-vacuole-during-host-cell-infection
#6
Marcell Crispim, Flávia Silva Damasceno, Agustín Hernández, María Julia Barisón, Ismael Pretto Sauter, Raphael Souza Pavani, Alexandre Santos Moura, Elizabeth Mieko Furusho Pral, Mauro Cortez, Maria Carolina Elias, Ariel Mariano Silber
Trypanosoma cruzi, the etiological agent of Chagas disease, consumes glucose and amino acids depending on the environmental availability of each nutrient during its complex life cycle. For example, amino acids are the major energy and carbon sources in the intracellular stages of the T. cruzi parasite, but their consumption produces an accumulation of NH4+ in the environment, which is toxic. These parasites do not have a functional urea cycle to secrete excess nitrogen as low-toxicity waste. Glutamine synthetase (GS) plays a central role in regulating the carbon/nitrogen balance in the metabolism of most living organisms...
January 10, 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29313410/ulk1-phosphorylates-ser30-of-becn1-in-association-with-atg14-to-stimulate-autophagy-induction
#7
Ji-Man Park, Minchul Seo, Chang Hwa Jung, Douglas Grunwald, Matthew Stone, Neil Michael Otto, Erik Toso, Yeseul Ahn, Michael Kyba, Timothy J Griffin, LeeAnn Higgins, Do-Hyung Kim
ULK1 (unc51-like autophagy activating kinase 1) is a serine/threonine kinase that plays a key role in regulating macroautophagy/autophagy induction in response to amino acid starvation. Despite the recent progress in understanding ULK1 functions, the molecular mechanism by which ULK1 regulates the induction of autophagy remains elusive. In this study, we determined that ULK1 phosphorylates Ser30 of BECN1 (beclin 1) in association with ATG14 (autophagy related 14) but not with UVRAG (UV radiation resistance associated)...
January 9, 2018: Autophagy
https://www.readbyqxmd.com/read/29305624/evidence-of-a-liver-alpha-cell-axis-in-humans-hepatic-insulin-resistance-attenuates-relationship-between-fasting-plasma-glucagon-and-glucagonotropic-amino-acids
#8
Nicolai J Wewer Albrechtsen, Kristine Færch, Troels M Jensen, Daniel R Witte, Jens Pedersen, Yuvaraj Mahendran, Anna E Jonsson, Katrine D Galsgaard, Marie Winther-Sørensen, Signe S Torekov, Torsten Lauritzen, Oluf Pedersen, Filip K Knop, Torben Hansen, Marit E Jørgensen, Dorte Vistisen, Jens J Holst
AIMS/HYPOTHESIS: The secretion of glucagon is controlled by blood glucose and inappropriate secretion of glucagon contributes to hyperglycaemia in diabetes. Besides its role in glucose regulation, glucagon regulates amino acid metabolism in hepatocytes by increasing ureagenesis. Disruption of this mechanism causes hyperaminoacidaemia, which in turn increases glucagon secretion. We hypothesised that hepatic insulin resistance (secondary to hepatic steatosis) via defective glucagon signalling/glucagon resistance would lead to impaired ureagenesis and, hence, increased plasma concentrations of glucagonotropic amino acids and, subsequently, glucagon...
January 5, 2018: Diabetologia
https://www.readbyqxmd.com/read/29303508/glutamine-synthetase-mediates-sorafenib-sensitivity-in-%C3%AE-catenin-active-hepatocellular-carcinoma-cells
#9
Bo Hwa Sohn, In Young Park, Ji-Hyun Shin, Sun Young Yim, Ju-Seog Lee
The gene encoding β-catenin is frequently mutated in hepatocellular carcinoma cells. While the oncogenicity of β-catenin has been extensively studied, β-catenin's role in hepatocellular carcinoma tumor metabolism is currently less well understood. In this study, we found that β-catenin regulates the expression of glutamine synthetase and triggers a series of metabolic changes leading to induction of autophagy in hepatocellular carcinoma cells. β-Catenin-active Hep3B and HepG2 cells exhibited higher basal levels of autophagic activity than did β-catenin wild-type cells...
January 5, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29296771/red-blood-cells-in-hemorrhagic-shock-a-critical-role-for-glutaminolysis-in-fueling-alanine-transamination-in-rats
#10
Julie A Reisz, Anne L Slaughter, Rachel Culp-Hill, Ernest E Moore, Christopher C Silliman, Miguel Fragoso, Erik D Peltz, Kirk C Hansen, Anirban Banerjee, Angelo D'Alessandro
Red blood cells (RBCs) are the most abundant host cell in the human body and play a critical role in oxygen transport and systemic metabolic homeostasis. Hypoxic metabolic reprogramming of RBCs in response to high-altitude hypoxia or anaerobic storage in the blood bank has been extensively described. However, little is known about the RBC metabolism following hemorrhagic shock (HS), the most common preventable cause of death in trauma, the global leading cause of total life-years lost. Metabolomics analyses were performed through ultra-high pressure liquid chromatography-mass spectrometry on RBCs from Sprague-Dawley rats undergoing HS (mean arterial pressure [MAP], <30 mm Hg) in comparison with sham rats (MAP, >80 mm Hg)...
July 25, 2017: Blood Advances
https://www.readbyqxmd.com/read/29295643/the-genomic-landscape-of-two-burkitt-lymphoma-cases-and-derived-cell-lines-comparison-between-primary-and-relapse-samples
#11
Claudia M Wever, Dominique Geoffrion, Bruno M Grande, Stephen Yu, Miguel Alcaide, Maryse Lemaire, Yasser Riazalhosseini, Josée Hébert, Christina Gavino, Donald C Vinh, Tina Petrogiannis-Haliotis, Svetlana Dmitrienko, Koren K Mann, Ryan D Morin, Nathalie A Johnson
Relapse occurs in 10-40% of Burkitt lymphoma (BL) patients that have completed intensive chemotherapy regimens and is typically fatal. While treatment-naive BL has been characterized, the genomic landscape of BL at the time of relapse (rBL) has never been reported. Here, we present a genomic characterization of two rBL patients. The diagnostic samples had mutations common in BL, including MYC and CCND3. Additional mutations were detected at relapse, affecting important pathways such as NFκB (IKBKB) and MEK/ERK (NRAS) signaling, glutamine metabolism (SIRT4), and RNA processing (ZFP36L2)...
January 3, 2018: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29290982/glucose-6-phosphate-dehydrogenase-and-transketolase-modulate-breast-cancer-cell-metabolic-reprogramming-and-correlate-with-poor-patient-outcome
#12
Adrián Benito, Ibrahim H Polat, Véronique Noé, Carlos J Ciudad, Silvia Marin, Marta Cascante
The pentose phosphate pathway is a fundamental metabolic pathway that provides cells with ribose and NADPH required for anabolic reactions - synthesis of nucleotides and fatty acids - and maintenance of intracellular redox homeostasis. It plays a key role in tumor metabolic reprogramming and has been reported to be deregulated in different types of tumors. Herein, we silenced the most important enzymes of this pathway - glucose-6-phosphate dehydrogenase (G6PD) and transketolase (TKT) - in the human breast cancer cell line MCF7...
December 5, 2017: Oncotarget
https://www.readbyqxmd.com/read/29279396/protonation-state-of-glutamate-73-regulates-the-formation-of-a-specific-dimeric-association-of-mvdac1
#13
Lucie A Bergdoll, Michael T Lerch, John W Patrick, Kendrick Belardo, Christian Altenbach, Paola Bisignano, Arthur Laganowsky, Michael Grabe, Wayne L Hubbell, Jeff Abramson
The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC's role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has been implicated with these processes. Herein, we report a specific pH-dependent dimerization of murine VDAC1 (mVDAC1) identified by double electron-electron resonance and native mass spectrometry...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29278688/stage-specific-metabolic-features-of-differentiating-neurons-implications-for-toxicant-sensitivity
#14
Johannes Delp, Simon Gutbier, Martin Cerff, Christin Zasada, Sebastian Niedenführ, Liang Zhao, Lena Smirnova, Thomas Hartung, Hanna Borlinghaus, Falk Schreiber, Jörg Bergemann, Jochem Gätgens, Martin Beyss, Salah Azzouzi, Tanja Waldmann, Stefan Kempa, Katharina Nöh, Marcel Leist
Developmental neurotoxicity (DNT) may be induced when chemicals disturb a key neurodevelopmental process, and many tests focus on this type of toxicity. Alternatively, DNT may occur when chemicals are cytotoxic only during a specific neurodevelopmental stage. The toxicant sensitivity is affected by the expression of toxicant targets and by resilience factors. Although cellular metabolism plays an important role, little is known how it changes during human neurogenesis, and how potential alterations affect toxicant sensitivity of mature vs...
December 24, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29276856/cellular-origin-of-18f-fdg-pet-imaging-signals-during-ceftriaxone-stimulated-glutamate-uptake-astrocytes-and-neurons
#15
Gerald A Dienel, Kevin L Behar, Douglas L Rothman
Ceftriaxone stimulates astrocytic uptake of the excitatory neurotransmitter glutamate, and it is used to treat glutamatergic excitotoxicity that becomes manifest during many brain diseases. Ceftriaxone-stimulated glutamate transport was reported to drive signals underlying [18F]fluorodeoxyglucose-positron emission tomographic ([18F]FDG-PET) metabolic images of brain glucose utilization and interpreted as supportive of the notion of lactate shuttling from astrocytes to neurons. This study draws attention to critical roles of astrocytes in the energetics and imaging of brain activity, but the results are provocative because (1) the method does not have cellular resolution or provide information about downstream pathways of glucose metabolism, (2) neuronal and astrocytic [18F]FDG uptake were not separately measured, and (3) strong evidence against lactate shuttling was not discussed...
December 1, 2017: Neuroscientist: a Review Journal Bringing Neurobiology, Neurology and Psychiatry
https://www.readbyqxmd.com/read/29274472/protein-phosphatase-2ac%C3%AE-gene-knock-out-results-in-cortical-atrophy-through-activating-hippo-cascade-in-neuronal-progenitor-cells
#16
Bo Liu, Li-Hua Sun, Yan-Fei Huang, Li-Jun Guo, Li-Shu Luo
Protein phosphatase 2ACα (PP2ACα), a vital member of the protein phosphatase family, has been studied primarily as a regulator for the development, growth and protein synthesis of a lot of cell types. Dysfunction of PP2ACα protein results in neurodegenerative disease; however, this finding has not been directly confirmed in the mouse model with PP2ACα gene knock-out. Therefore, in this study presented here, we generated the PP2ACα gene knock-out mouse model by the Cre-loxP targeting gene system, with the purpose to directly observe the regulatory role of PP2ACα gene in the development of mouse's cerebral cortex...
December 20, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/29274402/proteome-analysis-of-an-escherichia-coli-ptsn-null-strain-under-different-nitrogen-regimes
#17
Fernanda Gravina, Heloisa S Sanchuki, Thiago E Rodrigues, Edileusa C M Gerhardt, Fábio O Pedrosa, Emanuel M Souza, Gláucio Valdameri, Gustavo A de Souza, Luciano F Huergo
The carbohydrate-uptake phosphorelay PTS system plays a key role in metabolic regulation in Bacteria controlling the utilization of secondary carbon sources. Some bacteria, such as Escherichia coli, encode a paralogous system named PTSNtr (nitrogen related PTS). PTSNtr is composed of EINtr (ptsP), NPr (ptsO), and EIIANtr (ptsN). These proteins act as a phosphorelay system from phosphoenolpyruvate to EINtr, NPr and them to EIIANtr. PTSNtr is not involved in carbohydrate uptake and it may be dedicated to performing regulatory functions...
December 20, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29259131/identification-of-essential-amino-acids-for-glucose-transporter-5-glut5-mediated-fructose-transport
#18
Karolin Ebert, Maren Ewers, Ina Bisha, Simone Sander, Tanja Rasputniac, Hannelore Daniel, Iris Antes, Heiko Witt
Intestinal fructose uptake is mainly mediated by glucose transporter 5 (GLUT5/SLC2A5). Its closest relative, GLUT7, is also expressed in the intestine, but does not transport fructose. For rat Glut5, a change of glutamine to glutamic acid at codon 166 (p.Q166E) has been reported to alter substrate-binding specificity by shifting Glut5-mediated transport from fructose to glucose. Using chimeric proteins of GLUT5 and GLUT7, we here identified amino acid residues of GLUT5 that define its substrate specificity...
December 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29258187/usefulness-of-amino-acid-profiling-in-ovarian-cancer-screening-with-special-emphasis-on-their-role-in-cancerogenesis
#19
Szymon Plewa, Agnieszka Horała, Paweł Dereziński, Agnieszka Klupczynska, Ewa Nowak-Markwitz, Jan Matysiak, Zenon J Kokot
The aim of this study was to quantitate 42 serum-free amino acids, propose the biochemical explanation of their role in tumor development, and identify new ovarian cancer (OC) biomarkers for potential use in OC screening. The additional value of this work is the schematic presentation of the interrelationship between metabolites which were identified as significant for OC development and progression. The liquid chromatography-tandem mass spectrometry technique using highly-selective multiple reaction monitoring mode and labeled internal standards for each analyzed compound was applied...
December 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29248444/excitotoxicity-in-encephalopathy-associated-with-stec-o-157-infection
#20
Shigenobu Ishida, Kumi Yasukawa, Mai Koizumi, Katsuhiro Abe, Nozomi Hirai, Takafumi Honda, Hiroshi Sakuma, Hiroko Tada, Jun-Ichi Takanashi
Cytokines play an important role in the pathogenesis of the severe complications of Shiga toxin-producing Escherichia coli (STEC) infection, such as hemolytic uremic syndrome (HUS) and acute encephalopathy. A 3-year-old boy with acute encephalopathy associated with STEC O-157 HUS showed increased levels of IL-6 and IL-10, which normalized after methylprednisolone pulse therapy, and additionally exhibited a transient increase of glutamine on MR spectroscopy. This finding suggests that excitotoxicity, in addition to hypercytokinemia, may play an important role in the pathogenesis of HUS encephalopathy...
December 13, 2017: Brain & Development
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