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Ana Carla Peixoto Guissoni, Célia Maria Almeida Soares, Kareem R Badr, Fabiola Sousa Ficcadori, Ana Flávia Alves Parente, Juliana Alves Parente, Lilian Cristina Baeza, Menira Souza, Divina das Dores de Paula Cardoso
Human Adenoviruses (HAdVs) are etiological agents of different syndromes such as gastroenteritis, cystitis, ocular, and respiratory diseases, and infection by these viruses may cause alterations in cellular homeostasis. The objective of the study was the proteomic analysis of A-549 cells infected with HAdV-40 using LC-MS. At 30 h of infection, the quantitative analysis revealed 336 differentially expressed proteins. From them, 206 were induced (up-regulated) and 130 were suppressed (down-regulated). The majority of up-regulated proteins were related to energy, cellular organization, stress response, and apoptosis pathways...
March 15, 2018: Virus Genes
Jilong Zhou, Chengyu Li, Wang Yao, Alsiddig M A, Lijun Huo, Honglin Liu, Yi-Liang Miao
Autophagy is an essential cellular mechanism that degrades cytoplasmic proteins and organelles to recycle their components. Here we showed that autophagy was essential for the glycolysis switch and energy homeostasis in mouse granulosa cells (MGCs) under hypoxic condition. Our data indicated that hypoxia inducible factor-1α (HIF-1α) could be largely increased in developing follicles and this remarkable upregulation of HIF-1α triggered cell autophagy and glucose uptake. We found that blocking autophagy by Atg7 knockdown and 3-methyladenine (3-MA) treatment affected the glucose metabolism, with increased glycolytic enzyme activity and decreased ATP production...
March 13, 2018: Biology of Reproduction
Jun-Ho Cho, Goo-Young Kim, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia) is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC), a key enzyme in endogenous glucose production. This autosomal recessive disorder is characterized by impaired glucose homeostasis and long-term complications of hepatocellular adenoma/carcinoma (HCA/HCC). We have shown that hepatic G6Pase-α deficiency-mediated steatosis leads to defective autophagy that is frequently associated with carcinogenesis. We now show that hepatic G6Pase-α deficiency also leads to enhancement of hepatic glycolysis and hexose monophosphate shunt (HMS) that can contribute to hepatocarcinogenesis...
March 12, 2018: Biochemical and Biophysical Research Communications
Alexandra J Harvey, Carmel O'Brien, Jack Lambshead, John R Sheedy, Joy Rathjen, Andrew L Laslett, David K Gardner
Reprogramming somatic cells to a pluripotent cell state (induced Pluripotent Stem (iPS) cells) requires reprogramming of metabolism to support cell proliferation and pluripotency, most notably changes in carbohydrate turnover that reflect a shift from oxidative to glycolytic metabolism. Some aspects of iPS cell metabolism differ from embryonic stem (ES) cells, which may reflect a parental cell memory, or be a consequence of the reprogramming process. In this study, we compared the metabolism of 3 human iPS cell lines to assess the fidelity of metabolic reprogramming...
2018: PloS One
Natthakan Thongon, Chiara Zucal, Vito Giuseppe D'Agostino, Toma Tebaldi, Silvia Ravera, Federica Zamporlini, Francesco Piacente, Ruxanda Moschoi, Nadia Raffaelli, Alessandro Quattrone, Alessio Nencioni, Jean-Francois Peyron, Alessandro Provenzani
Background: Inhibitors of nicotinamide phosphoribosyltransferase (NAMPT), the rate-limiting enzyme in NAD+ biosynthesis from nicotinamide, exhibit anticancer effects in preclinical models. However, continuous exposure to NAMPT inhibitors, such as FK866, can induce acquired resistance. Methods: We developed FK866-resistant CCRF-CEM (T cell acute lymphoblastic leukemia) and MDA MB231 (breast cancer) models, and by exploiting an integrated approach based on genetic, biochemical, and genome wide analyses, we annotated the drug resistance mechanisms...
2018: Cancer & Metabolism
Jessica N R Peoples, Timmi Maxmillian, Quynh Le, Sergiy M Nadtochiy, Paul S Brookes, George A Porter, Victor L Davidson, Steven N Ebert
Cardiac energy demands during early embryonic periods are sufficiently met through glycolysis, but as development proceeds, oxidative phosphorylation in mitochondria becomes increasingly vital. Adrenergic hormones are known to stimulate metabolism in adult mammals and are essential for embryonic development, but relatively little is known about their effects on metabolism in the embryonic heart.  Here, we show that embryos lacking adrenergic stimulation have approximately 10-fold less cardiac ATP compared to littermate controls...
March 14, 2018: Journal of Biological Chemistry
Silvia Ravera, Maria Grazia Signorello, Martina Bartolucci, Sara Ferrando, Lucia Manni, Federico Caicci, Daniela Calzia, Isabella Panfoli, Alessandro Morelli, Giuliana Leoncini
BACKGROUND INFORMATION: Energy demand in human platelets is very high, to carry out their functions. As for most human cells, the aerobic metabolism represents the primary energy source in platelets, even though mitochondria are negligibly represented. Following the hypothesis that other structures could be involved in chemical energy production, in this work, we have investigated the functional expression of an extramitochondrial aerobic metabolism in platelets. RESULTS: Oximetric and luminometric analyses showed that platelets consume large amounts of oxygen and produce ATP in the presence of common respiring substrates, such as pyruvate + malate or succinate, although morphological electron microscopy analysis showed that these contain few mitochondria...
March 14, 2018: Biology of the Cell
A C Van Erp, R A Rebolledo, D Hoeksma, N R Jespersen, P J Ottens, R Nørregaard, M Pedersen, C Laustsen, J G M Burgerhof, J C Wolters, J Ciapaite, H E Bøtker, H G D Leuvenink, B Jespersen
Hepatic and renal energy status prior to transplantation correlates with graft survival. However, effects of brain death (BD) on organ-specific energy status are largely unknown. We studied metabolism, perfusion, oxygen consumption, and mitochondrial function in the liver and kidneys following BD. BD was induced in mechanically-ventilated rats, inflating an epidurally-placed Fogarty-catheter, with sham-operated rats as controls. A 9.4T-preclinical MRI system measured hourly oxygen availability (BOLD-related R2*) and perfusion (T1-weighted)...
March 13, 2018: Scientific Reports
Jue Hou, Joshua Williams, Elliot Botvinick, Eric Potma, Bruce J Tromberg
Label-free non-linear optical microscopy (NLOM) based on two-photon excited fluorescence (TPEF) from cofactors Nicotinamide Adenine Dinucleotide (NADH) and Flavin Adenine Dinucleotide (FAD+) is widely used for high-resolution cellular redox imaging. In this work, we combined three, label-free NLOM imaging methods to quantitatively characterize breast cancer cells and their relative invasive potential: 1) TPEF optical redox ratio (ORR = FAD+/NADH + FAD+), 2) coherent Raman scattering (CRS) of cellular lipids, and 3) second harmonic generation (SHG) of extracellular matrix (ECM) collagen...
March 13, 2018: Cancer Research
Avshalom Leibowitz, Ariel Bier, Mayan Gilboa, Edna Peleg, Iris Barshack, Ehud Grossman
Recent data indicate that artificial sweeteners (AS) may have deleterious effects on glucose metabolism. The purpose of this study was to compare the effects of AS and the effects of a high fructose diet (HFrD) on glucose metabolism and insulin resistance (IR) in Sprague-Dawley (SD) rats. SD rats were fed either regular chow, chow with saccharin (Sac) (0.1 mg/mL) placed in their water, or HFrD for seven weeks. Glucose, insulin, and triglycerides (Tg) levels were measured upon completion. A homeostatic model assessment (HOMA)-IR index was used to determine insulin resistance...
March 12, 2018: Nutrients
Ye Kuang, Xiaoyun Han, Mu Xu, Qing Yang
Most cancer cells perform glycolysis despite having sufficient oxygen. The specific metabolic pathways of cancer cells have become the focus of cancer treatment. Recently, accumulating evidence indicates oxidative phosphorylation (OXPHOS) and glycolysis can be regulated with each other. Thus, we suggest that the glycolysis of cancer cells is inhibited by restoring or improving OXPHOS in cancer cells. In our study, we found that oxaloacetate (OA) induced apoptosis in HepG2 cells in vivo and in vitro. Meanwhile, we found that OA induced a decrease in the energy metabolism of HepG2 cells...
March 13, 2018: Cancer Medicine
Penghui Wang, Lulu Jiang, Yang Cao, Xiaodan Zhang, Bangjing Chen, Shiyu Zhang, Ke Huang, Deyong Ye, Lu Zhou
Phosphoglycerate mutase 1 (PGAM1) is a glycolytic enzyme that dynamically converts 3-phosphoglycerate (3PG) to 2-phosphoglycerate (2PG), which was upregulated to coordinate glycolysis, pentose phosphate pathway (PPP) and serine biosynthesis to promote cancer cell proliferation and tumor growth in a variety of cancers. However, only a few inhibitors of PGAM1 have been reported with poor molecular or cellular efficacy. In this paper, a series of xanthone derivatives were discovered as novel PGAM1 inhibitors through scaffold hopping and sulfonamide reversal strategy based on the lead compound PGMI-004A...
February 24, 2018: Bioorganic & Medicinal Chemistry
Man K S Lee, Annas Al-Sharea, Dragana Dragoljevic, Andrew J Murphy
PURPOSE OF REVIEW: Hematopoietic stem cells (HSCs) reside in the bone marrow and are important in replenishing all cells in the blood through a process termed hematopoiesis. One of the defining characteristics of HSCs is that they must be able to balance their self-renewal capacity with their differentiation into committed blood cells in various blood lineages. For these events to occur, HSCs must be tightly regulated in the bone marrow by intrinsic and extrinsic factors to maintain steady hematopoiesis...
March 9, 2018: Current Opinion in Lipidology
O Villafraz, R Rondón-Mercado, A J Cáceres, J L Concepción, W Quiñones
T. rangeli epimastigotes contain only a single detectable phosphoglycerate kinase (PGK) enzyme in their cytosol. However, analysis of this parasite's recently sequenced genome showed a gene predicted to code for a PGK with the same molecular mass as the natural enzyme, and with a cytosolic localization as well. In this work, we have partially purified the natural PGK from T. rangeli epimastigotes. Furthermore, we cloned the predicted PGK gene and expressed it as a recombinant active enzyme. Both purified enzymes were kinetically characterized and displayed similar substrate affinities, with KmATP values of 0...
March 8, 2018: Experimental Parasitology
Hao Shi, Alexander Munk, Thomas S Nielsen, Morgan R Daughtry, Louise Larsson, Shize Li, Kasper F Høyer, Hannah W Geisler, Karolina Sulek, Rasmus Kjøbsted, Taylor Fisher, Marianne M Andersen, Zhengxing Shen, Ulrik K Hansen, Eric M England, Zhiyong Cheng, Kurt Højlund, Jørgen F P Wojtaszewski, Xiaoyong Yang, Matthew W Hulver, Richard F Helm, Jonas T Treebak, David E Gerrard
OBJECTIVE: Given that cellular O-GlcNAcylation levels are thought to be real-time measures of cellular nutrient status and dysregulated O-GlcNAc signaling is associated with insulin resistance, we evaluated the role of O-GlcNAc transferase (OGT), the enzyme that mediates O-GlcNAcylation, in skeletal muscle. METHODS: We assessed O-GlcNAcylation levels in skeletal muscle from obese, type 2 diabetic people, and we characterized muscle-specific OGT knockout (mKO) mice in metabolic cages and measured energy expenditure and substrate utilization pattern using indirect calorimetry...
February 24, 2018: Molecular Metabolism
Rita Rahmeh, Abrar Akbar, Mohamed Kishk, Thanyan Al Onaizi, Aisha Al-Shatti, Anisha Shajan, Batool Akbar, Salwa Al-Mutairi, Awatef Yateem
Food safety has become an issue of great interest worldwide. Listeria monocytogenes is a food-borne pathogen that causes listeriosis and is difficult to control in the dairy industry. The use of lactic acid bacteria (LAB) and their antimicrobial substances against Listeria is promising in food applications. Here, we report the isolation from raw camel milk of LAB displaying antilisterial activity. Two isolates were selected for their secretion of bacteriocin(s) and identified by 16S rRNA sequencing as Enterococcus faecium S6 and R9...
March 7, 2018: Journal of Dairy Science
Mehmet E Yalvac, Jakkrit Amornvit, Lei Chen, Kimberly M Shontz, Sarah Lewis, Zarife Sahenk
Neurotrophin 3 (NT-3) has well-recognized effects on peripheral nerve and Schwann cells, promoting axonal regeneration and associated myelination. In this study, we assessed the effects of AAV.NT-3 gene therapy on the oxidative state of the neurogenic muscle from the TremblerJ (TrJ ) mice at 16 weeks post-gene injection and found that the muscle fiber size increase was associated with a change in the oxidative state of muscle fibers towards normalization of the fiber type ratio seen in the wild type. NT-3-induced fiber size increase was most prominent for the fast twitch glycolytic fiber population...
March 9, 2018: Gene Therapy
Amy F Martinez, Samuel S McCachren, Marianne Lee, Helen A Murphy, Caigang Zhu, Brian T Crouch, Hannah L Martin, Alaattin Erkanli, Narasimhan Rajaram, Kathleen A Ashcraft, Andrew N Fontanella, Mark W Dewhirst, Nirmala Ramanujam
Many cancers adeptly modulate metabolism to thrive in fluctuating oxygen conditions; however, current tools fail to image metabolic and vascular endpoints at spatial resolutions needed to visualize these adaptations in vivo. We demonstrate a high-resolution intravital microscopy technique to quantify glucose uptake, mitochondrial membrane potential (MMP), and SO2 to characterize the in vivo phentoypes of three distinct murine breast cancer lines. Tetramethyl rhodamine, ethyl ester (TMRE) was thoroughly validated to report on MMP in normal and tumor-bearing mice...
March 8, 2018: Scientific Reports
Maria Carolina Costa Melo Svidnicki, Andrey Santos, Jhonathan Angel Araujo Fernandez, Ana Paula Hitomi Yokoyama, Isis Quezado Magalhães, Vitoria Regia Pereira Pinheiro, Silvia Regina Brandalise, Paulo Augusto Achucarro Silveira, Fernando Ferreira Costa, Sara Teresinha Olalla Saad
BACKGROUND: Pyruvate kinase deficiency is a hereditary disease that affects the glycolytic pathway of the red blood cell, causing nonspherocytic hemolytic anemia. The disease is transmitted as an autosomal recessive trait and shows a marked variability in clinical expression. This study reports on the molecular characterization of ten Brazilian pyruvate kinase-deficient patients and the genotype-phenotype correlations. METHOD: Sanger sequencing and in silico analysis were carried out to identify and characterize the genetic mutations...
January 2018: Revista Brasileira de Hematologia e Hemoterapia
Maia Kavanagh Williamson, Naomi Coombes, Florian Juszczak, Marios Athanasopoulos, Mariam B Khan, Thomas R Eykyn, Ushani Srenathan, Leonie S Taams, Julianna Dias Zeidler, Andrea T Da Poian, Hendrik Huthoff
Infection of primary CD4+ T cells with HIV-1 coincides with an increase in glycolysis. We investigated the expression of glucose transporters (GLUT) and glycolytic enzymes in human CD4+ T cells in response to infection with HIV-1. We demonstrate the co-expression of GLUT1, GLUT3, GLUT4, and GLUT6 in human CD4+ T cells after activation, and their concerted overexpression in HIV-1 infected cells. The investigation of glycolytic enzymes demonstrated activation-dependent expression of hexokinases HK1 and HK2 in human CD4+ T cells, and a highly significant increase in cellular hexokinase enzyme activity in response to infection with HIV-1...
March 7, 2018: Viruses
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