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https://www.readbyqxmd.com/read/28820579/site-specific-conjugation-to-native-and-engineered-lysines-in-human-immunoglobulins-by-microbial-transglutaminase
#1
Jared Spidel, Benjamin Vaessen, Earl Albone, Xin Cheng, Arielle Verdi, J Bradford Kline
The use of microbial transglutaminase (MTG) to produce site-specific antibody-drug conjugates (ADCs) has thus far focused on transamidation of engineered acyl donor glutamine residues in an antibody based on the hypothesis that the lower specificity of MTG for acyl acceptor lysines may result in transamidation of multiple native lysine residues, thereby yielding heterogeneous products. We investigated the utilization of native IgG lysines as acyl acceptor sites for glutamine-based acyl donor substrates. Of the approximately 80 lysines in multiple recombinant IgG monoclonal antibodies (mAbs), none were transamidated...
August 18, 2017: Bioconjugate Chemistry
https://www.readbyqxmd.com/read/28818367/metabolic-features-involved-in-drought-stress-tolerance-mechanisms-in-peanut-nodules-and-their-contribution-to-biological-nitrogen-fixation
#2
Ana Laura Furlan, Eliana Bianucci, Stella Castro, Karl-Josef Dietz
Legumes belong to the most important crops worldwide. They increase soil fertility due their ability to establish symbiotic associations with soil microorganisms, known as rhizobia, capable of fixing nitrogen from the atmosphere. However, they are frequently exposed to abiotic stress conditions in particular drought. Such adverse conditions impair the biological nitrogen fixation (BNF) and depend largely on the legume. Therefore, two peanut cultivars with contrasting tolerance to drought, namely the more tolerant EC-98 and the sensitive Granoleico, were investigated to elucidate the relative contribution of BNF to the tolerance to drought...
October 2017: Plant Science: An International Journal of Experimental Plant Biology
https://www.readbyqxmd.com/read/28816396/identification-of-novel-site-specific-alterations-in-the-modification-level-of-myelin-basic-protein-isolated-from-mouse-brain-at-different-ages-using-capillary-electrophoresis-mass-spectrometry
#3
Bettina Sarg, Klaus Faserl, Herbert H Lindner
Myelin basic protein (MBP) is a multifunctional protein involved in maintaining the stability and integrity of the myelin sheath by a variety of interactions with membranes and other proteins. MBP is subjected to extensive post-translational modifications (PTMs) that are known to be crucial for the regulation of these interactions. Here we report capillary electrophoresis-mass spectrometric (CE-MS) analysis for the separation and identification of MBP peptides that incorporate the same PTM at different sites, creating multiple localization variants, and the ability to analyze challenging modifications such as asparagine and glutamine deamidation, isomerization and arginine citrullination...
August 17, 2017: Proteomics
https://www.readbyqxmd.com/read/28816095/new-astroglial-injury-defined-biomarkers-for-neurotrauma-assessment
#4
Julia Halford, Sean Shen, Kyohei Itamura, Jaclynn Levine, Albert C Chong, Gregg Czerwieniec, Thomas C Glenn, David A Hovda, Paul Vespa, Ross Bullock, W Dalton Dietrich, Stefania Mondello, Joseph A Loo, Ina-Beate Wanner
Traumatic brain injury (TBI) is an expanding public health epidemic with pathophysiology that is difficult to diagnose and thus treat. TBI biomarkers should assess patients across severities and reveal pathophysiology, but currently, their kinetics and specificity are unclear. No single ideal TBI biomarker exists. We identified new candidates from a TBI CSF proteome by selecting trauma-released, astrocyte-enriched proteins including aldolase C (ALDOC), its 38kD breakdown product (BDP), brain lipid binding protein (BLBP), astrocytic phosphoprotein (PEA15), glutamine synthetase (GS) and new 18-25kD-GFAP-BDPs...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28814091/the-effect-of-vitamin-d-on-mcf-7-breast-cancer-cell-metabolism
#5
B Saracligil, B Ozturk, A Unlu, S Abusoglu, G Tekin
The role of vitamin D in calcium absorption and bone health is known. The studies revealed that vitamin D modulates breast cancer cell growth and it is also associated with a reduced breast cancer risk. The primary objective of this study was to highlight the metabolic effect of Vitamin D on MCF-7 breast cancer cell line. For that purpose, we checked the apoptosis, energy, amino-acid and acylcarnitine levels in cancer cells, that the study propose, that 1α, 25(OH)2D3 could inhibit cell growth in a dose and time dependent manner...
2017: Bratislavské Lekárske Listy
https://www.readbyqxmd.com/read/28813676/pharmacologic-or-genetic-targeting-of-glutamine-synthetase-skews-macrophages-toward-an-m1-like-phenotype-and-inhibits-tumor-metastasis
#6
Erika M Palmieri, Alessio Menga, Rosa Martín-Pérez, Annamaria Quinto, Carla Riera-Domingo, Giacoma De Tullio, Douglas C Hooper, Wouter H Lamers, Bart Ghesquière, Daniel W McVicar, Attilio Guarini, Massimiliano Mazzone, Alessandra Castegna
Glutamine-synthetase (GS), the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR) activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28813658/ccctc-binding-factor-translates-interleukin-2-and-%C3%AE-ketoglutarate-sensitive-metabolic-changes-in-t%C3%A2-cells-into-context-dependent-gene-programs
#7
Danielle A Chisolm, Daniel Savic, Amanda J Moore, Andre Ballesteros-Tato, Beatriz León, David K Crossman, Cornelis Murre, Richard M Myers, Amy S Weinmann
Despite considerable research connecting cellular metabolism with differentiation decisions, the underlying mechanisms that translate metabolite-sensitive activities into unique gene programs are still unclear. We found that aspects of the interleukin-2 (IL-2)-sensitive effector gene program in CD4(+) and CD8(+) T cells in type 1 conditions (Th1) were regulated by glutamine and alpha-ketoglutarate (αKG)-induced events, in part through changes in DNA and histone methylation states. We further identified a mechanism by which IL-2- and αKG-sensitive metabolic changes regulated the association of CCCTC-binding factor (CTCF) with select genomic sites...
August 15, 2017: Immunity
https://www.readbyqxmd.com/read/28812766/modulatory-effects-of-arginine-glutamine-and-branched-chain-amino-acids-on-heat-shock-proteins-immunity-and-antioxidant-response-in-exercised-rats
#8
Carolina Soares Moura, Pablo Christiano Barboza Lollo, Priscila Neder Morato, Eder Muller Risso, Jaime Amaya-Farfan
Heat shock proteins (HSPs) are endogenous proteins whose function is to maintain the cell's tolerance to insult, and glutamine supplementation is known to increase HSP expression during intense exercise. Since few studies have addressed the possibility that supplementation with other amino acids could have similar effects to that of glutamine, our objective was to evaluate the effects of leucine, valine, isoleucine and arginine as potential stimulators of HSPs 25, 60, 70 and 90 in rats subjected to acute exercise as a stressing factor...
August 16, 2017: Food & Function
https://www.readbyqxmd.com/read/28812298/a-gata-type-transcription-factor-acareb-for-nitrogen-metabolism-is-involved-in-regulation-of-cephalosporin-biosynthesis-in-acremonium-chrysogenum
#9
Feifei Guan, Yuanyuan Pan, Jinyang Li, Gang Liu
In filamentous fungi, nitrogen metabolism is repressed by GATA-type zinc finger transcription factors. Nitrogen metabolite repression has been found to affect antibiotic production, but the mechanism is still poorly understood. AcareB, encoding a homologue of fungal GATA-type regulatory protein, was cloned from Acremonium chrysogenum. Gene disruption and genetic complementation demonstrated that AcareB plays a key role in utilization of ammonium, glutamine and urea. In addition, significant reduction of cephalosporin production in the AcareB disruption mutant indicated that AcareB is important for cephalosporin production...
August 14, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/28811348/a-critical-role-of-glutamine-and-asparagine-%C3%AE-nitrogen-in-nucleotide-biosynthesis-in-cancer-cells-hijacked-by-an-oncogenic-virus
#10
Ying Zhu, Tingting Li, Suzane Ramos da Silva, Jae-Jin Lee, Chun Lu, Hyungjin Eoh, Jae U Jung, Shou-Jiang Gao
While glutamine is a nonessential amino acid that can be synthesized from glucose, some cancer cells primarily depend on glutamine for their growth, proliferation, and survival. Numerous types of cancer also depend on asparagine for cell proliferation. The underlying mechanisms of the glutamine and asparagine requirement in cancer cells in different contexts remain unclear. In this study, we show that the oncogenic virus Kaposi's sarcoma-associated herpesvirus (KSHV) accelerates the glutamine metabolism of glucose-independent proliferation of cancer cells by upregulating the expression of numerous critical enzymes, including glutaminase 2 (GLS2), glutamate dehydrogenase 1 (GLUD1), and glutamic-oxaloacetic transaminase 2 (GOT2), to support cell proliferation...
August 15, 2017: MBio
https://www.readbyqxmd.com/read/28811139/metabonomics-approach-to-assessing-the-metabolism-variation-and-gender-gap-of-drosophila-melanogaster-in-aging-process
#11
Yu-Zhi Zhou, Ming-Liang Yan, Li Gao, Jian-Qin Zhang, Xue-Mei Qin, Xiang Zhang, Guan-Hua Du
Drosophila melanogaster is increasingly used for study aging mechanism and evaluating anti-aging drugs, but the changes of metabolites and differences of metabolites change between male and female during the aging process are not well known. Metabolomics technology, a massive information provider, has promoted the understanding of metabolic profile and overall changes of metabolites in organism. In this study, (1)H NMR based metabonomics was employed to investigate the dynamic changes of metabolites in whole bodies of male and female Drosophila melanogaster at 3, 15, 30, 45days and to research the gender gap of metabolites changes in aging process...
August 12, 2017: Experimental Gerontology
https://www.readbyqxmd.com/read/28810585/glutamine-promotes-hsp70-and-inhibits-%C3%AE-synuclein-accumulation-in-pheochromocytoma-pc12-cells
#12
Haiyang Wang, Chongyang Tang, Zhenfeng Jiang, Xiao Zhou, Jianhang Chen, Meng Na, Hong Shen, Zhiguo Lin
Hsp70 regulates α-Synuclein (α-Syn) degeneration in Parkinson's disease (PD), indicating that Hsp70 promotion may be able to prevent or reverse α-Syn-induced toxicity in PD. Additionally, it has been demonstrated that glutamine (Gln) enhances Hsp70 expression. In the present study, Gln-induced Hsp70 promotion in pheochromocytoma was investigated with reverse transcription- quantitative polymerase chain reaction and western blotting methods. Then it was observed whether heat shock factor (HSF)-1 was required for this phenomenon with an RNA interference strategy...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28809118/glucose-limitation-alters-glutamine-metabolism-in-muc1-overexpressing-pancreatic-cancer-cells
#13
Teklab Gebregiworgis, Vinee Purohit, Surendra K Shukla, Saber Tadros, Nina V Chaika, Jaime Abrego, Scott E Mulder, Venugopal Gunda, Pankaj K Singh, Robert Powers
Pancreatic cancer cells overexpressing MUC1 rely on aerobic glycolysis and, correspondingly, are dependent on glucose for survival. Our NMR metabolomics comparative analysis of control (S2-013.Neo) and MUC1-overexpressing (S2-013.MUC1) cells demonstrate that MUC1 reprograms glutamine metabolism upon glucose limitation. The observed alteration in glutamine metabolism under glucose limitation accompanied with a relative decrease in the proliferation of MUC1-overexpressing cells compared to steady state conditions...
August 15, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28808255/critical-role-for-arginase-2-in-obesity-associated-pancreatic-cancer
#14
Tamara Zaytouni, Pei-Yun Tsai, Daniel S Hitchcock, Cory D DuBois, Elizaveta Freinkman, Lin Lin, Vicente Morales-Oyarvide, Patrick J Lenehan, Brian M Wolpin, Mari Mino-Kenudson, Eduardo M Torres, Nicholas Stylopoulos, Clary B Clish, Nada Y Kalaany
Obesity is an established risk factor for pancreatic ductal adenocarcinoma (PDA). Despite recent identification of metabolic alterations in this lethal malignancy, the metabolic dependencies of obesity-associated PDA remain unknown. Here we show that obesity-driven PDA exhibits accelerated growth and a striking transcriptional enrichment for pathways regulating nitrogen metabolism. We find that the mitochondrial form of arginase (ARG2), which hydrolyzes arginine into ornithine and urea, is induced upon obesity, and silencing or loss of ARG2 markedly suppresses PDA...
August 14, 2017: Nature Communications
https://www.readbyqxmd.com/read/28805497/putative-role-of-glutamine-in-the-activation-of-cbl-cipk-signalling-pathways-during-salt-stress-in-sorghum
#15
Rafael de Souza Miranda, Juan Carlos Alvarez-Pizarro, José Hélio Costa, Stelamaris de Oliveira Paula, José Tarquinio Prisco, Enéas Gomes-Filho
The salt overly sensitive (SOS) pathway is the only mechanism known for Na(+) extrusion in plant cells. SOS pathway activation involves Ca(2+)-sensing proteins, such as calcineurin B-like (CBL) proteins, and CBL-interacting protein kinases (CIPKs). In this signalling mechanism, a transit increase in cytosolic Ca(2+) concentration triggered by Na(+) accumulation is perceived by CBL (also known as SOS3). Afterward, SOS3 physically interacts with a CIPK (also known as SOS2), forming the SOS2/SOS3 complex, which can regulate the number downstream targets, controlling ionic homeostasis...
August 14, 2017: Plant Signaling & Behavior
https://www.readbyqxmd.com/read/28804824/laboratory-testing-for-activated-protein-c-resistance-apcr
#16
Soma Mohammed, Emmanuel J Favaloro
Activated protein C resistance (APCR) describes a hemostatic disorder characterized by a poor anticoagulant response to activated protein C (APC). This results in an increased risk of venous thrombosis, including deep vein thrombosis and pulmonary embolism. Protein C is a natural anticoagulant that is synthesized in the liver and is activated to APC via proteolysis. APC then degrades Factors Va and VIIIa. APCR describes the reduced inability of APC to cleave Factors Va and VIIIa, which therefore promotes increased thrombin generation and potentially leads to a prothrombotic state...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28804556/anti-tumor-efficacy-evaluation-of-a-novel-monoclonal-antibody-targeting-neutral-amino-acid-transporter-asct2-using-patient-derived-xenograft-mouse-models-of-gastric-cancer
#17
Noriyuki Kasai, Aya Sasakawa, Kenta Hosomi, Tze Wei Poh, Bernadette Lynn Chua, Wei Peng Yong, Jimmy So, Shing Leng Chan, Richie Soong, Koji Kono, Toshihiko Ishii, Kazuya Yamano
ASC amino acid transporter 2 (ASCT2), also known as solute linked carrier family 1 member A5 (SLC1A5) is a Na+-dependent glutamine/neutral amino acid transporter. ASCT2 acts as a high-affinity transporter of L-glutamine (Gln) and has been reported to be up-regulated in a variety of cancerous tissues including stomach, liver, and kidney. In this study, we evaluated anti-tumor efficacy of a novel anti-ASCT2 humanized monoclonal antibody, KM8094, which has a neutralizing activity against glutamine uptake, as a therapeutic antibody against gastric cancer and explored clinical predictive biomarker candidates by utilizing patient-derived xenograft (PDX) mouse models...
2017: American Journal of Translational Research
https://www.readbyqxmd.com/read/28804500/pluripotent-stem-cell-metabolism-and-mitochondria-beyond-atp
#18
REVIEW
Jarmon G Lees, David K Gardner, Alexandra J Harvey
Metabolism is central to embryonic stem cell (ESC) pluripotency and differentiation, with distinct profiles apparent under different nutrient milieu, and conditions that maintain alternate cell states. The significance of altered nutrient availability, particularly oxygen, and metabolic pathway activity has been highlighted by extensive studies of their impact on preimplantation embryo development, physiology, and viability. ESC similarly modulate their metabolism in response to altered metabolite levels, with changes in nutrient availability shown to have a lasting impact on derived cell identity through the regulation of the epigenetic landscape...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28803850/association-of-exposure-to-manganese-and-iron-with-striatal-and-thalamic-gaba-and-other-neurometabolites-neuroimaging-results-from-the-weldox-ii-study
#19
Swaantje Casjens, Urike Dydak, Shalmali Dharmadhikari, Anne Lotz, Martin Lehnert, Clara Quetscher, Christoph Stewig, Benjamin Glaubitz, Tobias Schmidt-Wilcke, David Edmondson, Chien-Lin Yeh, Tobias Weiss, Christoph van Thriel, Lennard Herrmann, Siegfried Muhlack, Dirk Woitalla, Michael Aschner, Thomas Brüning, Beate Pesch
OBJECTIVE: Magnetic resonance spectroscopy (MRS) is a non-invasive method to quantify neurometabolite concentrations in the brain. Within the framework of the WELDOX II study, we investigated the association of exposure to manganese (Mn) and iron (Fe) with γ-aminobutyric acid (GABA) and other neurometabolites in the striatum and thalamus of 154 men. MATERIAL AND METHODS: GABA-edited and short echo-time MRS at 3T was used to assess brain levels of GABA, glutamate, total creatine (tCr) and other neurometabolites...
August 10, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28803777/paraoxonase-2-facilitates-pancreatic-cancer-growth-and-metastasis-by-stimulating-glut1-mediated-glucose-transport
#20
Arvindhan Nagarajan, Shaillay Kumar Dogra, Lisha Sun, Neeru Gandotra, Thuy Ho, Guoping Cai, Gary Cline, Priti Kumar, Robert A Cowles, Narendra Wajapeyee
Metabolic deregulation is a hallmark of human cancers, and the glycolytic and glutamine metabolism pathways were shown to be deregulated in pancreatic ductal adenocarcinoma (PDAC). To identify new metabolic regulators of PDAC tumor growth and metastasis, we systematically knocked down metabolic genes that were overexpressed in human PDAC tumor samples using short hairpin RNAs. We found that p53 transcriptionally represses paraoxonase 2 (PON2), which regulates GLUT1-mediated glucose transport via stomatin. The loss of PON2 initiates the cellular starvation response and activates AMP-activated protein kinase (AMPK)...
August 17, 2017: Molecular Cell
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