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Glutamine AND beta cells

Rupert Laurenz Mayer, Josef D Schwarzmeier, Marlene C Gerner, Andrea Bileck, Johanna C Mader, Samuel M Meier-Menches, Samuel M Gerner, Klaus G Schmetterer, Tobias Pukrop, Albrecht Reichle, Astrid Slany, Christopher Gerner
B cell chronic lymphocytic leukemia (B-CLL), the most common type of leukemia in adults, is still essentially incurable despite the development of novel therapeutic strategies. This reflects the incomplete understanding of the pathophysiology of this disease. A comprehensive proteome analysis of primary human B-CLL cells and B cells from younger as well as elderly healthy donors was performed. For comparison, also the chronic B cell leukemia cell line JVM-13 was included. A principal component analysis comprising 6945 proteins separated these four groups, placing B cells of aged-matched controls between those of young donors and B-CLL patients, while identifying JVM-13 as poorly related cells...
December 1, 2017: Molecular & Cellular Proteomics: MCP
Grace Onimoe, Genine Smarzo
Sickle cell disease (SCD) is caused by a mutation in the sixth codon of the β-globin gene on chromosome 11, which leads to a single amino acid substitution (glutamine to valine). Sickle-(δβ)(0)-thalassemia is a rare variant of sickle cell disease (delta-beta thalassemia occurring in association with sickle hemoglobin, HbS), sparsely reported in literature, and has been associated with symptomatology necessitating careful monitoring and follow-up. We describe a patient who presented with a newborn screen reported as "FS" and a negative family history for sickle cell disease and sickle cell trait...
2017: Case Reports in Hematology
Jitka Soukupova, Andrea Malfettone, Petra Hyroššová, María-Isabel Hernández-Alvarez, Irene Peñuelas-Haro, Esther Bertran, Alexandra Junza, Jordi Capellades, Gianluigi Giannelli, Oscar Yanes, Antonio Zorzano, José Carlos Perales, Isabel Fabregat
Transforming Growth Factor beta (TGF-β) induces tumor cell migration and invasion. However, its role in inducing metabolic reprogramming is poorly understood. Here we analyzed the metabolic profile of hepatocellular carcinoma (HCC) cells that show differences in TGF-β expression. Oxygen consumption rate (OCR), extracellular acidification rate (ECAR), metabolomics and transcriptomics were performed. Results indicated that the switch from an epithelial to a mesenchymal/migratory phenotype in HCC cells is characterized by reduced mitochondrial respiration, without significant differences in glycolytic activity...
October 2, 2017: Scientific Reports
Mariagrazia Grimaldi, Melis Karaca, Livia Latini, Estelle Brioudes, Thomas Schalch, Pierre Maechler
Congenital hyperinsulinism/hyperammonemia (HI/HA) syndrome gives rise to unregulated protein-induced insulin secretion from pancreatic beta-cells, fasting hypoglycemia and elevated plasma ammonia levels. Mutations associated with HI/HA were identified in the Glud1 gene, encoding for glutamate dehydrogenase (GDH). We aimed at identifying the molecular causes of dysregulation in insulin secretion and ammonia production conferred by the most frequent HI/HA mutation Ser445Leu. Following transduction with adenoviruses carrying the human GDH-wild type or GDH-S445L-mutant gene, immunoblotting showed efficient expression of the transgenes in all the investigated cell types...
September 15, 2017: Human Molecular Genetics
Stefano Caruso, Julien Calderaro, Eric Letouzé, Jean-Charles Nault, Gabrielle Couchy, Anaïs Boulai, Alain Luciani, Elie-Serge Zafrani, Paulette Bioulac-Sage, Olivier Seror, Sandrine Imbeaud, Jessica Zucman-Rossi
BACKGROUND & AIMS: Growing evidence suggests that genetic predisposition significantly increases the risk of hepatocellular carcinoma (HCC), independently from the presence of other risk factors. Here, we report a novel germline DICER1 mutation associated with familial recurrent liver tumors. We then aimed to investigate the contribution of constitutional and somatic DICER1 mutations on HCC occurrence. METHODS: We investigated two individuals of a single family that developed recurrent well-differentiated hepatocellular tumors over the years...
December 22, 2016: Journal of Hepatology
Veli Bakalov, Roland Amathieu, Mohamed N Triba, Marie-Jeanne Clément, Laura Reyes Uribe, Laurence Le Moyec, Ata Murat Kaynar
Patients surviving sepsis demonstrate sustained inflammation, which has been associated with long-term complications. One of the main mechanisms behind sustained inflammation is a metabolic switch in parenchymal and immune cells, thus understanding metabolic alterations after sepsis may provide important insights to the pathophysiology of sepsis recovery. In this study, we explored metabolomics in a novel Drosophila melanogaster model of surviving sepsis using Nuclear Magnetic Resonance (NMR), to determine metabolite profiles...
December 21, 2016: Metabolites
Sharada H Sharma, Senthilkumar Thulasingam, David Raj Chellappan, Prabu Chinnaswamy, Sangeetha Nagarajan
Targeting tumor metabolism by natural products is a novel approach and provides rationale for anti-cancer drug discovery. The present study aims to explore the impact of morin and/or esculetin on c-myc induced energy metabolism in 1,2-dimethylhydrazine (DMH) induced colon cancer in rats. In order to achieve this aim we analyzed the expression of glucose and glutamine transporters and the key enzymes of glycolytic pathway besides the markers of neoplastic changes viz., mucin depleted foci (MDF), beta catenin accumulated crypts (BCAC), and markers of cell proliferation viz...
February 5, 2017: European Journal of Pharmacology
Young Hye Song, Christine Warncke, Sung Jin Choi, Siyoung Choi, Aaron E Chiou, Lu Ling, Han-Yuan Liu, Susan Daniel, Marc A Antonyak, Richard A Cerione, Claudia Fischbach
Adipose-derived stem cells (ASCs) are abundantly present in the mammary microenvironment and can promote breast cancer malignancy by differentiating into myofibroblasts. However, it remains largely unclear which role tumor-derived extracellular vesicles (TEVs) play in this process. Here, we used microfabricated, type I collagen-based 3-D tissue culture platforms to investigate the effect of breast cancer cell-derived TEVs on ASCs myofibroblast differentiation and consequential changes in extracellular matrix remodeling and vascular sprouting...
July 2017: Matrix Biology: Journal of the International Society for Matrix Biology
Christoph Tappeiner, Ellinor Maurer, Pauline Sallin, Thomas Bise, Volker Enzmann, Markus Tschopp
In contrast to the mammalian retina, the zebrafish retina exhibits the potential for lifelong retinal neurogenesis and regeneration even after severe damage. Previous studies have shown that the transforming growth factor beta (TGFβ) signaling pathway is activated during the regeneration of different tissues in the zebrafish and is needed for regeneration in the heart and the fin. In this study, we have investigated the role of the TGFβ pathway in the N-methyl-N-nitrosourea (MNU)-induced chemical model of rod photoreceptor de- and regeneration in adult zebrafish...
2016: PloS One
Hao Zhang, Weipeng Su, Zhixiong Ying, Yueping Chen, Le Zhou, Yue Li, Jingfei Zhang, Lili Zhang, Tian Wang
PURPOSE: The objective of the present study was to test the hypothesis that N-acetylcysteine (NAC) may play beneficial roles against intrauterine growth retardation (IUGR)-induced hepatic damage in suckling piglets. METHODS: Fourteen IUGR and seven normal birth weight (NBW) neonatal male piglets were selected. Piglets were weaned at 7 days of postnatal age and fed the control formula milk (NBW-CON and IUGR-CON groups) or the control formula milk supplemented with 1...
October 8, 2016: European Journal of Nutrition
Fabiana K Ludka, Maurício P Cunha, Tharine Dal-Cim, Luisa Bandeira Binder, Leandra C Constantino, Caio M Massari, Wagner C Martins, Ana Lúcia S Rodrigues, Carla I Tasca
Intracerebroventricular (icv) amyloid-beta (Aβ)1-40 infusion to mice has been demonstrated to cause neurotoxicty and depressive-like behavior and it can be used to evaluate antidepressant and neuroprotective effect of drugs. Atorvastatin is a widely used statin that has demonstrated antidepressant-like effect in predictable animal behavioral models and neuroprotective effect against Aβ1-40 infusion. The purpose of this study was to determine the effect of in vivo atorvastatin treatment against Aβ1-40-induced changes in mood-related behaviors and biochemical parameters in ex vivo hippocampal slices from mice...
October 5, 2016: Molecular Neurobiology
Chelsea M Griffith, Mi-Xin Xie, Wen-Ying Qiu, Andrew A Sharp, Chao Ma, Aihua Pan, Xiao-Xin Yan, Peter R Patrylo
Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by beta-amyloid (Aβ) deposition, neurofibrillary tangles and cognitive decline. Recent pharmacologic studies have found that ATP-sensitive potassium (KATP) channels may play a role in AD and could be a potential therapeutic target. Interestingly, these channels are found in both neurons and astrocytes. One of the hallmarks associated with AD is reactive gliosis and a change in astrocytic function has been identified in several neuropathological conditions including AD...
November 12, 2016: Neuroscience
Lu An, Paul M Harrison
BACKGROUND: Prions are proteinaceous particles that propagate alternative protein conformations/states to further copies of the same proteins, and are transmitted from cell-to-cell, and organism-to-organism. Prions are usually made of the beta-sheet rich assemblies termed amyloid. The original prion protein PrP causes devastating neurodegenerative disorders in humans and other mammals. In the yeast Saccharomyces cerevisiae, many prion-forming proteins have been observed; a prominent feature of these proteins is an intrinsically disordered domain rich in glutamine (Q) and asparagine (N) residues...
2016: Biology Direct
Ramesh Katam, Katsumi Sakata, Prashanth Suravajhala, Tibor Pechan, Devaiah M Kambiranda, Karamthot Sivasankar Naik, Baozhu Guo, Sheikh M Basha
UNLABELLED: Water stress (WS) predisposes peanut plants to fungal infection resulting in pre-harvest aflatoxin contamination. Major changes during water stress including oxidative stress, lead to destruction of photosynthetic apparatus and other macromolecules within cells. Two peanut cultivars with diverse drought tolerance characteristics were subjected to WS, and their leaf proteome was compared using two-dimensional electrophoresis complemented with MALDI-TOF/TOF mass spectrometry...
June 30, 2016: Journal of Proteomics
Arnulf H Koeppen, R Liane Ramirez, Alyssa B Becker, Joseph E Mazurkiewicz
INTRODUCTION: Dorsal root ganglia (DRG) are highly vulnerable to frataxin deficiency in Friedreich ataxia (FA), an autosomal recessive disease due to pathogenic homozygous guanine-adenine-adenine trinucleotide repeat expansions in intron 1 of the FXN gene (chromosome 9q21.11). An immunohistochemical and immunofluorescence study of DRG in 15 FA cases and 12 controls revealed that FA causes major primary changes in satellite cells and inflammatory destruction of neurons. A panel of antibodies was used to reveal the cytoplasm of satellite cells (glutamine synthetase, S100, metabotropic glutamate receptors 2/3, excitatory amino acid transporter 1, ATP-sensitive inward rectifier potassium channel 10, and cytosolic ferritin), gap junctions (connexin 43), basement membranes (laminin), mitochondria (ATP synthase subunit beta and frataxin), and monocytes (CD68 and IBA1)...
May 3, 2016: Acta Neuropathologica Communications
Laleh Shariati, Mehran Modaress, Hossein Khanahmad, Zahra Hejazi, Mohammad Amin Tabatabaiefar, Mansoor Salehi, Mohammad Hossein Modarressi
OBJECTIVE: To compare methods for erythroid differentiation of K562 cells that will be promising in the treatment of beta-thalassemia by inducing γ-globin synthesis. RESULTS: Cells were treated separately with: RPMI 1640 medium without glutamine, RPMI 1640 medium without glutamine supplemented with 1 mM sodium butyrate, RPMI 1640 medium supplemented with 1 mM sodium butyrate, 25 µg cisplatin/ml, 0.1 µg cytosine arabinoside/ml. The highest differentiation (84 %) with minimum toxicity was obtained with cisplatin at 15 µg /ml...
August 2016: Biotechnology Letters
Marina Delic-Sarac, Selma Mutevelic, Jasenko Karamehic, Djemo Subasic, Tomislav Jukic, Jozo Coric, Ognjen Ridjic, Mirsad Panjeta, Lejla Zunic
INTRODUCTION: Anti GAD (antibodies on glutamic acid decarboxylase) and anti-IA2 antibodies (against tyrosine phosphatase), today, have their place and importance in diagnosis and prognosis of Type 1 diabetes. Huge number of patients with diabetes mellitus type 1 have these antibodies. Insulin antibodies are of critical importance in diagnosis of diabetes mellitus type 1 for pediatric population. MATERIALS AND METHODS: During 2014, the samples of 80 patients from Clinical Center University Sarajevo (CCUS) Pediatrics clinic's, Endocrinology department were analyzed on anti-GAD and IA2 antibodies...
February 2016: Acta Informatica Medica: AIM
Wangfei Wang, Constance J Jeffery
Proteins expressed on the bacterial cell surface play important roles in infection and virulence and can be targets for vaccine development or used as biomarkers. Surprisingly, an increasing number of surface proteins are being found to be identical to intracellular enzymes and chaperones, and a few dozen intracellular/surface moonlighting proteins have been found that have different functions inside the cell and on the cell surface. The results of twenty-two published bacterial surface proteomics studies were analyzed using bioinformatics tools to consider how many additional intracellular proteins are also found on the cell surface...
April 26, 2016: Molecular BioSystems
K S Antonets, K V Volkov, A L Maltseva, L M Arshakian, A P Galkin, A A Nizhnikov
Amyloids are protein fibrils adopting structure of cross-beta spine exhibiting either pathogenic or functionally significant properties. In prokaryotes, there are several groups of functional amyloids; however, all of them were identified by specialized approaches that do not reveal all cellular amyloids. Here, using our previously developed PSIA (Proteomic Screening and Identification of Amyloids) approach, we have conducted a proteomic screening for candidates for novel amyloid-forming proteins in Escherichia coli as one of the most important model organisms and biotechnological objects...
January 2016: Biochemistry. Biokhimii︠a︡
Lu An, David Fitzpatrick, Paul M Harrison
BACKGROUND: Prions are transmissible, propagating alternative states of proteins, and are usually made from the fibrillar, beta-sheet-rich assemblies termed amyloid. Prions in the budding yeast Saccharomyces cerevisiae propagate heritable phenotypes, uncover hidden genetic variation, function in large-scale gene regulation, and can act like diseases. Almost all these amyloid prions have asparagine/glutamine-rich (N/Q-rich) domains. Other proteins, that we term here 'prionogenic amyloid formers' (PAFs), have been shown to form amyloid in vivo, and to have N/Q-rich domains that can propagate heritable states in yeast cells...
2016: BMC Evolutionary Biology
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