Read by QxMD icon Read


Beiqing Wu, Jianhui Liu, Runze Zhao, Yuju Li, Justin Peer, Alexander L Braun, Lixia Zhao, Yi Wang, Zenghan Tong, Yunlong Huang, Jialin C Zheng
BACKGROUND: Extracellular vesicles (EVs) are important in the intercellular communication of the central nervous system, and their release is increased during neuroinflammation. Our previous data demonstrated an increased release of EVs during HIV-1 infection and immune activation in glial cells. However, the molecular mechanism by which infection and inflammation increase EV release remains unknown. In the current study, we investigated the role of glutaminase 1 (GLS1)-mediated glutaminolysis and the production of a key metabolic intermediate α-ketoglutarate on EV release...
March 14, 2018: Journal of Neuroinflammation
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
Marina Wright Muelas, Fernando Ortega, Rainer Breitling, Claus Bendtsen, Hans V Westerhoff
Optimization of experimental conditions is critical in ensuring robust experimental reproducibility. Through detailed metabolomic analysis we found that cell culture conditions significantly impacted on glutaminase (GLS1) sensitivity resulting in variable sensitivity and irreproducibility in data. Baseline metabolite profiling highlighted that untreated cells underwent significant changes in metabolic status. Both the extracellular levels of glutamine and lactate and the intracellular levels of multiple metabolites changed drastically during the assay...
February 14, 2018: Scientific Reports
Irfana Soomro, Ying Sun, Zhai Li, Lonnette Diggs, Georgia Hatzivassiliou, Ajit G Thomas, Rana Rais, Barbara S Slusher, Stefan Somlo, Edward Y Skolnik
Background: Metabolism of glutamine by glutaminase 1 (GLS1) plays a key role in tumor cell proliferation via the generation of ATP and intermediates required for macromolecular synthesis. We hypothesized that glutamine metabolism also plays a role in proliferation of autosomal-dominant polycystic kidney disease (ADPKD) cells and that inhibiting GLS1 could slow cyst growth in animal models of ADPKD. Methods: Primary normal human kidney and ADPKD human cyst-lining epithelial cells were cultured in the presence or absence of two pharmacologic inhibitors of GLS1, bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide 3 (BPTES) and CB-839, and the effect on proliferation, cyst growth in collagen and activation of downstream signaling pathways were assessed...
February 5, 2018: Nephrology, Dialysis, Transplantation
Najat O Hamed, Laila-Al-Ayadhi, Mohamed A Osman, Elkhawad Abdalla O, Hanan Qasem, Majida Al-Marshoud, Nada M Merghani, Afaf El-Ansary
BACKGROUND: AIM: Autism is a heterogeneous neurological disorder that is characterized by impairments in communication and social interactions, repetitive behaviors and sensory abnormalities. The etiology of autism remains unclear. Animal, genetic and postmortem studies suggest that an imbalance exists in the neuronal excitation and inhibition (E/I) system in autism. The aim of this study was to determine whether alterations of the measured parameters in children with autism are significantly associated with the risk of a sensory dysfunction...
January 22, 2018: Psychiatry and Clinical Neurosciences
Karen Bernard, Naomi J Logsdon, Gloria A Benavides, Yan Sanders, Jianhua Zhang, Victor M Darley-Usmar, Victor J Thannickal
Myofibroblasts participate in physiological wound healing and pathological fibrosis. Myofibroblast differentiation is characterized by the expression of α-smooth muscle actin and extracellular matrix proteins and is dependent on metabolic reprogramming. In this study, we explored the role of glutaminolysis and metabolites of TCA in supporting myofibroblast differentiation. Glutaminolysis converts Gln into α-ketoglutarate (α-KG), a critical intermediate in the TCA cycle. Increases in the steady-state concentrations of TCA cycle metabolites including α-KG, succinate, fumarate, malate, and citrate were observed in TGF-β1-differentiated myofibroblasts...
January 26, 2018: Journal of Biological Chemistry
Zi-Yan Liu, Hai-Tang Wang, Jing Tang, Zai-Sheng Qin
OBJECTIVE: To investigate whether RhoA/Rho-kinase contributes to the occurrence of chronic post-thoracotomy pain (CPSP) by up regulation of glutaminase 1 (GLS1) expression in the spinal dorsal cord. METHODS: Twenty five male Sprague Dawley (SD) rats were divided into control group (n=5) and model group (n=20). The rats in the model group were randomized into two sub groups (n=10) for observation on day 10 and day 21 after thoracotomy, and each group was further divided into CPSP and non CPSP groups according to the behavioral test results...
October 20, 2017: Nan Fang Yi Ke da Xue Xue Bao, Journal of Southern Medical University
Nicola J Curtis, Lorraine Mooney, Lorna Hopcroft, Filippos Michopoulos, Nichola Whalley, Haihong Zhong, Clare Murray, Armelle Logie, Mitchell Revill, Kate F Byth, Amanda D Benjamin, Mike A Firth, Stephen Green, Paul D Smith, Susan E Critchlow
Tumors frequently display a glycolytic phenotype with increased flux through glycolysis and concomitant synthesis of lactate. To maintain glycolytic flux and prevent intracellular acidification, tumors efflux lactate via lactate transporters (MCT1-4). Inhibitors of lactate transport have the potential to inhibit glycolysis and tumor growth. We developed a small molecule inhibitor of MCT1 (AZD3965) and assessed its activity across a panel of cell lines. We explored its antitumor activity as monotherapy and in combination with doxorubicin or rituximab...
September 19, 2017: Oncotarget
Sarah Beaudin, JoEllen Welsh
Genomic profiling has identified a subset of metabolic genes that are altered by 1,25-dihydroxyvitamin D (1,25D) in breast cells, including GLUL, the gene that encodes glutamine synthetase (GS). In this study, we explored the relevance of vitamin D modulation of GLUL and other metabolic genes in the context of glutamine utilization and dependence. We show that exposure of breast epithelial cells to glutamine deprivation or a GS inhibitor reduced growth and these effects were exacerbated by cotreatment with 1,25D...
December 1, 2017: Endocrinology
Jing Ge, Huachun Cui, Na Xie, Sami Banerjee, Sijia Guo, Shubham Dubey, Stephen Barnes, Gang Liu
Glutaminolysis is the metabolic process of glutamine, of which aberration has been implicated in several pathogeneses. While we and others recently found a diversity of metabolic dysregulations in organ fibrosis, it is unknown if glutaminolysis regulates the pro-fibrotic activities of myofibroblasts, the primary effector in this pathology. In this study, we found that lung myofibroblasts demonstrated significantly augmented glutaminolysis that was mediated by elevated Glutaminase 1 (Gls1). Inhibition of glutaminolysis by specific Gls1 inhibitors CB-839 and BPTES as well as Gls1 siRNA blunted the expression of collagens, but not that of Fibronectin, Elastin or myofibroblastic marker smooth muscle actin α (SMA-α)...
October 11, 2017: American Journal of Respiratory Cell and Molecular Biology
Ajit S Divakaruni, Alexander Y Andreyev, George W Rogers, Anne N Murphy
Activities of enzymes localized to the mitochondrial matrix of mammalian cells are often critical regulatory steps in cellular metabolism. As such, measurement of matrix enzyme activities in response to genetic modifications or drug interventions is often desired. However, measurements in intact cells are often hampered by the presence of other isozymes in the cytoplasm as well as the inability to deliver enzyme substrates across cellular membranes. Classic approaches to liberate matrix enzymes utilize harsh treatments that disrupt intracellular architecture or require significant starting material to allow mitochondrial isolation prior to sample extraction...
October 4, 2017: Analytical Biochemistry
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
Zhou Song, Bo Wei, Canrong Lu, Peiyu Li, Lin Chen
Cancer cells remodel their metabolic programs towards aerobic glycolysis and elevated glutaminolysis to meet the requirement s of rapid proliferation. Understanding how cells sense and adapt to these changes may provide new targets for therapeutic intervention. Deamination of glutamine to glutamate by glutaminase (GLS1) is an essential step in glutaminolysis. The present study revealed that the loss of GLS1 expression by RNA interference or inhibitor decreased the proliferation and viability of colorectal cancer (CRC) cells...
September 2017: Oncology Letters
Hongling Huang, Saar Vandekeere, Joanna Kalucka, Laura Bierhansl, Annalisa Zecchin, Ulrike Brüning, Asjad Visnagri, Nadira Yuldasheva, Jermaine Goveia, Bert Cruys, Katleen Brepoels, Sabine Wyns, Stephen Rayport, Bart Ghesquière, Stefan Vinckier, Luc Schoonjans, Richard Cubbon, Mieke Dewerchin, Guy Eelen, Peter Carmeliet
Endothelial cell (EC) metabolism is emerging as a regulator of angiogenesis, but the precise role of glutamine metabolism in ECs is unknown. Here, we show that depriving ECs of glutamine or inhibiting glutaminase 1 (GLS1) caused vessel sprouting defects due to impaired proliferation and migration, and reduced pathological ocular angiogenesis. Inhibition of glutamine metabolism in ECs did not cause energy distress, but impaired tricarboxylic acid (TCA) cycle anaplerosis, macromolecule production, and redox homeostasis...
August 15, 2017: EMBO Journal
Yi Wang, Yuju Li, Runze Zhao, Beiqing Wu, Blaise Lanoha, Zenghan Tong, Justin Peer, Jianhui Liu, Huangui Xiong, Yunlong Huang, Jialin Zheng
Glutaminolysis, a metabolic process that converts glutamine to glutamate, is particularly important for the central nervous system since glutamate is the major transmitter of excitatory synapses. Glutaminase is the mitochondrial enzyme that catalyzes the first step of glutaminolysis. Two genes encode at least four isoforms of glutaminase in humans. Gls1 gene encodes isoforms kidney-type glutaminase (KGA) and glutaminase C (GAC) through alternative splicing, whereas Gls2 gene encodes liver-type glutaminase isoforms...
November 2017: Brain, Behavior, and Immunity
Teng-Kuang Yeh, Ching-Chuan Kuo, Yue-Zhi Lee, Yi-Yu Ke, Kuang-Feng Chu, Hsing-Yu Hsu, Hsin-Yu Chang, Yu-Wei Liu, Jen-Shin Song, Cheng-Wei Yang, Li-Mei Lin, Manwu Sun, Szu-Huei Wu, Po-Chu Kuo, Chuan Shih, Chiung-Tong Chen, Lun Kelvin Tsou, Shiow-Ju Lee
Humans have two glutaminase genes, GLS (GLS1) and GLS2, each of which has two alternative transcripts: the kidney isoform (KGA) and glutaminase C (GAC) for GLS, and the liver isoform (LGA) and glutaminase B (GAB) for GLS2. Initial hit compound (Z)-5-((1-(4-bromophenyl)-2,5-dimethyl-1H-pyrrol-3-yl)methylene)thiazolidine-2,4-dione (2), a thiazolidine-2,4-dione, was obtained from a high throughput screening of 40 000 compounds against KGA. Subsequently, a series of thiazolidine-2,4-dione derivatives was synthesized...
July 13, 2017: Journal of Medicinal Chemistry
Nicola J Curtis, Lorraine Mooney, Lorna Hopcroft, Filippos Michopoulos, Nichola Whalley, Haihong Zhong, Clare Murray, Armelle Logie, Mitchell Revill, Kate F Byth, Amanda D Benjamin, Mike A Firth, Stephen Green, Paul D Smith, Susan E Critchlow
Tumors frequently display a glycolytic phenotype with increased flux through glycolysis and concomitant synthesis of lactate. To maintain glycolytic flux and prevent intracellular acidification, tumors efflux lactate via lactate transporters (MCT1-4). Inhibitors of lactate transport have the potential to inhibit glycolysis and tumor growth. We developed a small molecule inhibitor of MCT1 (AZD3965) and assessed its activity across a panel of cell lines. We explored its antitumor activity as monotherapy and in combination with doxorubicin or rituximab...
May 25, 2017: Oncotarget
Man-Wook Hur, Jae-Hyeon Yoon, Min-Young Kim, Hyeonseok Ko, Bu-Nam Jeon
Kr-POK (ZBTB7c) is a kidney cancer-related POK transcription factor that not only represses transcription of CDKN1A but also increases expression of FASN. However, precisely how Kr-POK affects cell metabolism by controlling gene expression in response to an energy source in rapidly proliferating cells remains unknown. In this study, we characterized the molecular and functional features of Kr-POK in the context of tumor growth and glutamine metabolism. We found that cells expressing Kr-POK shRNA exhibited more severe cell death than control cells in glucose-deprived medium, and that knockdown of Kr-POK decreased glutamine uptake...
August 2017: Biochimica et Biophysica Acta
Wei-Qun Lu, Ying-Ying Hu, Xiao-Ping Lin, Wei Fan
Clinical treatment for colorectal cancer (CRC) thus far encounters a huge challenge due to oxaliplatin-resistance. As crucial rate-limiting enzymes in aerobic glycolysis and glutaminolysis, pyruvate kinase M2 type (PKM2) and kidney-type glutaminase (GLS1) are proposed to carry important implications in colorectal carcinogenesis and drug-resistance. This study aimed to explore the possible association of oxaliplatin-resistance with aerobic glycolysis/glutaminolysis indexed by PKM2/GLS1 expression. PKM2 and GLS1 expression was quantified by polymerase chain reaction (PCR) and Western blot techniques in CRC cell lines...
July 4, 2017: Oncotarget
Soshi Takahashi, Jun Saegusa, Sho Sendo, Takaichi Okano, Kengo Akashi, Yasuhiro Irino, Akio Morinobu
BACKGROUND: The recent findings of cancer-specific metabolic changes, including increased glucose and glutamine consumption, have provided new therapeutic targets for consideration. Fibroblast-like synoviocytes (FLS) from rheumatoid arthritis (RA) patients exhibit several tumor cell-like characteristics; however, the role of glucose and glutamine metabolism in the aberrant proliferation of these cells is unclear. Here, we evaluated the role of these metabolic pathways in RA-FLS proliferation and in autoimmune arthritis in SKG mice...
April 11, 2017: Arthritis Research & Therapy
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"