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https://www.readbyqxmd.com/read/28627692/the-role-of-intestinal-endotoxemia-in-a-rat-model-of-aluminum-neurotoxicity
#1
Feng Wang, Rui-Xia Guo, Wen-Xing Li, Bao-Feng Yu, Bai Han, Li-Xin Liu, De-Wu Han
The present study aimed to investigate the effects of intestinal endotoxemia (IETM) in a rat model of aluminum neurotoxicity established by D-galactose and aluminum trichloride (AlCl3). Adult Wistar rats were administered D‑galactose and AlCl3 to create the aluminum neurotoxicity model. The learning and memory abilities of the rats were subsequently observed using a Morris water maze test and the serum levels of lipopolysaccharide (LPS), tumor necrosis factor (TNF)‑α, interleukin (IL)‑1, diamine oxidase (DAO), glutamine (Gln) and glutaminase were measured...
June 15, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28624534/glutaminase-c-overexpression-in-the-brain-induces-learning-deficits-synaptic-dysfunctions-and-neuroinflammation-in-mice
#2
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 and glutaminase C (GAC) through alternative splicing, whereas GLS2 gene encodes liver-type glutaminase isoforms...
June 14, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28614770/transcription-factor-gata3-expression-is-induced-by-gls2-overexpression-in-a-glioblastoma-cell-line-but-is-gls2-independent-in-patient-derived-glioblastoma
#3
E Majewska, R Rola, M Barczewska, J Marquez, J Albrecht, M Szeliga
Phosphate-activated glutaminase (GA), a ubiquitous glutamine-metabolizing enzyme, is encoded by two genes, GLS and GLS2. In mammalian cancers, GLS isoforms are perceived as molecules promoting cell proliferation and invasion, whereas the role of GLS2 isoforms seems to be more complex and cell type-specific. Previous studies have shown abundance of GLS and lack of GLS2 transcripts in T98G human glioblastoma (GBM) cell line and patient-derived GBM. Transfection with GAB sequence, the whole GLS2 cDNA transcript, suppressed malignant phenotype of T98G cells...
April 2017: Journal of Physiology and Pharmacology: An Official Journal of the Polish Physiological Society
https://www.readbyqxmd.com/read/28611197/treatment-of-pancreatic-cancer-patient-derived-xenograft-panel-with-metabolic-inhibitors-reveals-efficacy-of-phenformin
#4
N V Rajeshkumar, Shinichi Yabuuchi, Shweta Pai, Elizabeth De Oliveira, Jurre J Kamphorst, Joshua D Rabinowitz, Héctor Tejero, Fatima Al-Shahrour, Manuel Hidalgo, Anirban Maitra, Chi V Dang
Purpose: To identify effective metabolic inhibitors to suppress the aggressive growth of pancreatic ductal adenocarcinoma (PDAC), we explored the in vivo anti-tumor efficacy of metabolic inhibitors in a panel of patient-derived PDAC xenograft models (PDXs), and investigated whether genomic alterations of tumors correlate with the sensitivity to metabolic inhibitors. <p>Experimental Design: Mice with PDAC tumors from six to thirteen individual PDXs were randomized and treated, once daily for 4 weeks, with either PBS (vehicle) or the glutaminase inhibitor BPTES, transaminase inhibitor aminooxyacetate (AOA), pyruvate dehydrogenase kinase inhibitor dichloroacetate (DCA), autophagy inhibitor chloroquine (CQ), mitochondrial complex I inhibitor phenformin/metformin...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28609101/design-synthesis-and-evaluation-of-thiazolidine-2-4-dione-derivatives-as-a-novel-class-of-glutaminase-inhibitors
#5
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 (1), 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...
June 13, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28597996/sensitization-of-melanoma-cells-to-temozolomide-by-overexpression-of-microrna-203-through-direct-targeting-of-glutaminase-mediated-glutamine-metabolism
#6
X Chang, W Zhu, H Zhang, S Lian
BACKGROUND: Malignant melanoma (MM) is an aggressive malignancy, which accounts for 80% of skin cancer-related deaths and is notably resistant to conventional chemotherapeutic agents. One of the most common treatments for melanoma is surgery, followed by various combinations of chemotherapy drugs. AIM: To investigate the role of microRNA (miR)-203 in sensitivity of MM cells to the chemotherapy drug temozolomide (TMZ). METHODS: Using quantitative reverse transcription PCR, we measured the expression of miR-203 in an MM cell line...
June 9, 2017: Clinical and Experimental Dermatology
https://www.readbyqxmd.com/read/28596071/genetic-and-metabolic-engineering-approaches-for-the-production-and-delivery-of-l-asparaginases-an-overview
#7
REVIEW
Jalaja Vidya, Syed Sajitha, Mrudula Vasudevan Ushasree, Raveendran Sindhu, Parameswaran Binod, Aravind Madhavan, Ashok Pandey
L-asparaginase is one of the protein drugs for countering leukemia and lymphoma. A major challenge in the therapeutic potential of the enzyme is its immunogenicity, low-plasma half-life and glutaminase activity that are found to be the reasons for toxicities attributed to asparaginase therapy. For addressing these challenges, several research and developmental activities are going on throughout the world for an effective drug delivery for treatment of cancer. Hence there is an urgent need for the development of asparaginase with improved properties for efficient drug delivery...
May 12, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28578659/rapamycin-mtorc1-inhibitor-reduces-the-production-of-lactate-and-2-hydroxyglutarate-oncometabolites-in-idh1-mutant-fibrosarcoma-cells
#8
Zoltán Hujber, Gábor Petővári, Norbert Szoboszlai, Titanilla Dankó, Noémi Nagy, Csilla Kriston, Ildikó Krencz, Sándor Paku, Olivér Ozohanics, László Drahos, András Jeney, Anna Sebestyén
BACKGROUND: Multiple studies concluded that oncometabolites (e.g. D-2-hydroxyglutarate (2-HG) related to mutant isocitrate dehydrogenase 1/2 (IDH1/2) and lactate) have tumour promoting potential. Regulatory mechanisms implicated in the maintenance of oncometabolite production have great interest. mTOR (mammalian target of rapamycin) orchestrates different pathways, influences cellular growth and metabolism. Considering hyperactivation of mTOR in several malignancies, the question has been addressed whether mTOR operates through controlling of oncometabolite accumulation in metabolic reprogramming...
June 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28571744/kr-pok-zbtb7c-regulates-cancer-cell-proliferation-through-glutamine-metabolism
#9
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...
May 30, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28549811/recent-developments-in-l-glutaminase-production-and-applications-an-overview
#10
REVIEW
Parameswaran Binod, Raveendran Sindhu, Aravind Madhavan, Amith Abraham, Anil Kuruvilla Mathew, Ummalyma Sabeela Beevi, Rajeev K Sukumaran, Sudhir P Singh, Ashok Pandey
l-glutaminases is an important industrial enzyme which finds potential applications in different sectors ranging from therapeutic to food industry. It is widely distributed in bacteria, actinomycetes, yeast and fungi. l-Glutaminases are mostly produced by Bacillus and Pseudomonas sp. and few reports were available with fungal, actinomycete and yeast system. Modern biotechnological tools help in the improved production as well as with tailor made properties for specific applications. Most of the genetic engineering studies were carried out for the production of l-glutaminase with improved thermo-tolerance and salt tolerance...
May 15, 2017: Bioresource Technology
https://www.readbyqxmd.com/read/28535436/microcystin-lr-induces-changes-in-the-gaba-neurotransmitter-system-of-zebrafish
#11
Wei Yan, Li Li, Guangyu Li, Sujuan Zhao
It has been reported that exposure to microcystins altered adult zebrafish swimming performance parameters, but the possible mechanisms of action remain unknown. Neuronal activity depends on the balance between the number of excitatory and inhibitory processes which are associated with neurotransmitters. In the present study, zebrafish embryos (5 d post-fertilization) were exposed to 0, 0.3, 3 and 30μg/L (microcystin-LR) MCLR for 90day until reaching sexual maturity. To investigate the effects of MCLR on the neurotransmitter system, mRNA levels involved in amino acid g-aminobutyric acid (GABA) and glutamate metabolic pathways were tested using quantitative real-time PCR...
May 15, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/28526749/the-origin-and-evolution-of-human-glutaminases-and-their-atypical-c-terminal-ankyrin-repeats
#12
Camila Cristina Pascoal, Zeyaul Islam, Douglas Adamoski, Igor Monteze Ferreira, Ricardo Diogo Righetto, Jefferson Bettini, Rodrigo Villares Portugal, Wyatt W Yue, Ana Gonzalez, Sandra Martha Gomes Dias, Andre Luis Berteli Ambrosio
On the basis of tissue-specific enzyme activity and inhibition by catalytic products, Hans Krebs first demonstrated the existence of multiple glutaminases in mammals. Currently, two human genes are known to encode at least four glutaminase isoforms. However, the phylogeny of these medically relevant enzymes remains unclear, prompting us to investigate their origin and evolution. Using prokaryotic and eukaryotic glutaminase sequences, we built a phylogenetic tree whose topology suggested that the multidomain architecture was inherited from bacterial ancestors, probably simultaneously with the hosting of the proto-mitochondrion endosymbiont...
May 19, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28498807/knockdown-of-pkm2-and-gls1-expression-can-significantly-reverse-oxaliplatin-resistance-in-colorectal-cancer-cells
#13
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...
April 24, 2017: Oncotarget
https://www.readbyqxmd.com/read/28484941/proteomics-as-a-tool-to-identify-new-targets-against-aspergillus-and-scedosporium-in-the-context-of-cystic-fibrosis
#14
Andoni Ramirez-Garcia, Aize Pellon, Idoia Buldain, Aitziber Antoran, Aitana Arbizu-Delgado, Xabier Guruceaga, Aitor Rementeria, Fernando L Hernando
Cystic fibrosis (CF) is a genetic disorder that increases the risk of suffering microbial, including fungal, infections. In this paper, proteomics-based information was collated relating to secreted and cell wall proteins with potential medical applications from the most common filamentous fungi in CF, i.e., Aspergillus and Scedosporium/Lomentospora species. Among the Aspergillus fumigatus secreted allergens, β-1,3-endoglucanase, the alkaline protease 1 (Alp1/oryzin), Asp f 2, Asp f 13/15, chitinase, chitosanase, dipeptidyl-peptidase V (DppV), the metalloprotease Asp f 5, mitogillin/Asp f 1, and thioredoxin reductase receive a special mention...
May 8, 2017: Mycopathologia
https://www.readbyqxmd.com/read/28462847/breaking-the-ritual-metabolic-cycle-in-order-to-save-acetyl-coa-a-potential-role-for-mitochondrial-humanin-in-t2-bladder-cancer-aggressiveness
#15
Nesreen Nabil Omar, Reham Fathy Tash, Youssef Shoukry, Karim Omar ElSaeed
INTRODUCTION: Cancer cells may exhibit outsourcing of their high energy need in order to avoid the intrinsic mitochondrial apoptosis. Reduced mitochondrial respiration and accumulation of mitochondrial genome mutations are among metabolic transformations in this regard. Mitochondrial humanin (MT-RNR2) is a small peptide with anti-apoptotic activities attributed to binding some pro-apoptotic proteins. AIM OF THE WORK: The current study aims at investigating the expression of mitochondrial humanin in bladder tumor cells and the possible casting of humanin anti-apoptotic action through orchestrating some of the mitochondrial metabolic enzymes...
April 24, 2017: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/28439409/serial-deletion-reveals-structural-basis-and-stability-for-the-core-enzyme-activity-of-human-glutaminase-1-isoforms-relevance-to-excitotoxic-neurodegeneration
#16
Yuju Li, Justin Peer, Runze Zhao, Yinghua Xu, Beiqing Wu, Yi Wang, Changhai Tian, Yunlong Huang, Jialin Zheng
BACKGROUND: Glutaminase 1 is a phosphate-activated metabolic enzyme that catalyzes the first step of glutaminolysis, which converts glutamine into glutamate. Glutamate is the major neurotransmitter of excitatory synapses, executing important physiological functions in the central nervous system. There are two isoforms of glutaminase 1, KGA and GAC, both of which are generated through alternative splicing from the same gene. KGA and GAC both transcribe 1-14 exons in the N-terminal, but each has its unique C-terminal in the coding sequence...
2017: Translational Neurodegeneration
https://www.readbyqxmd.com/read/28427419/tnf-%C3%AE-promotes-extracellular-vesicle-release-in-mouse-astrocytes-through-glutaminase
#17
Kaizhe Wang, Ling Ye, Hongfang Lu, Huili Chen, Yanyan Zhang, Yunlong Huang, Jialin C Zheng
BACKGROUND: Extracellular vesicles (EVs) are membrane-contained vesicles shed from cells. EVs contain proteins, lipids, and nucleotides, all of which play important roles in intercellular communication. The release of EVs is known to increase during neuroinflammation. Glutaminase, a mitochondrial enzyme that converts glutamine to glutamate, has been implicated in the biogenesis of EVs. We have previously demonstrated that TNF-α promotes glutaminase expression in neurons. However, the expression and the functionality of glutaminase in astrocytes during neuroinflammation remain unknown...
April 20, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28416628/impaired-glutamatergic-neurotransmission-in-the-vmh-may-contribute-to-defective-counterregulation-in-recurrently-hypoglycemic-rats
#18
Golam M I Chowdhury, Peili Wang, Alisha Ciardi, Ramanaiah Mamillapalli, Justin Johnson, Wanling Zhu, Tore Eid, Kevin Behar, Owen Chan
The objectives of this study were to understand the role of ventromedial hypothalamic (VMH) glutamatergic neurotransmission in response to hypoglycemia and to elucidate the effects of recurrent hypoglycemia (RH) on this neurotransmitter. We measured 1) changes in interstitial VMH glutamate levels using microdialysis and biosensors, 2) identified the receptors that mediate glutamate's stimulatory effects on the counterregulatory responses, 3) quantified glutamate metabolic enzyme levels in the VMH, 4) examined astrocytic glutamate reuptake mechanisms and 5) used (1)H-[(13)C]-NMR spectroscopy to evaluate the effects of RH on neuronal glutamate metabolism...
April 17, 2017: Diabetes
https://www.readbyqxmd.com/read/28415782/glutaminase-inhibitor-cb-839-synergizes-with-carfilzomib-in-resistant-multiple-myeloma-cells
#19
Ravyn M Thompson, Dominik Dytfeld, Leticia Reyes, Reeder M Robinson, Brittany Smith, Yefim Manevich, Andrzej Jakubowiak, Mieczyslaw Komarnicki, Anna Przybylowicz-Chalecka, Tomasz Szczepaniak, Amit K Mitra, Brian G Van Ness, Magdalena Luczak, Nathan G Dolloff
Curative responses in the treatment of multiple myeloma (MM) are limited by the emergence of therapeutic resistance. To address this problem, we set out to identify druggable mechanisms that convey resistance to proteasome inhibitors (PIs; e.g., bortezomib), which are cornerstone agents in the treatment of MM. In isogenic pairs of PI sensitive and resistant cells, we observed stark differences in cellular bioenergetics between the divergent phenotypes. PI resistant cells exhibited increased mitochondrial respiration driven by glutamine as the principle fuel source...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28408540/small-kernel2-encodes-a-glutaminase-in-vitamin-b6-biosynthesis-essential-for-maize-seed-development
#20
Yan-Zhuo Yang, Shuo Ding, Yong Wang, Cui-Ling Li, Yun Shen, Robert Meeley, Donald R McCarty, Bao-Cai Tan
Vitamin B6, an essential cofactor for a range of biochemical reactions and a potent antioxidant, plays important roles in plant growth, development, and stress tolerance. Vitamin B6 deficiency causes embryo lethality in Arabidopsis (Arabidopsis thaliana), but the specific role of vitamin B6 biosynthesis in endosperm development has not been fully addressed, especially in monocot crops, where endosperm constitutes the major portion of the grain. Through molecular characterization of a small kernel2 (smk2) mutant in maize, we reveal that vitamin B6 has differential effects on embryogenesis and endosperm development in maize...
June 2017: Plant Physiology
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