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intracellular metabolism

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https://www.readbyqxmd.com/read/28933846/inhibition-of-calcium-dependent-protein-kinase-1-cdpk1-by-pyrazolopyrimidine-analogs-decreases-establishment-and-reoccurrence-of-central-nervous-system-disease-by-toxoplasma-gondii
#1
Florentine U Rutaganira, Jennifer Barks, Mary Savari Dhason, Qiuling Wang, Michael Steven Lopez, Shaojun Long, Joshua B Radke, Nathaniel G Jones, Amarendar R Maddirala, James W Janetka, Majida El Bakkouri, Raymond Hui, Kevan M Shokat, L David Sibley
Calcium dependent protein kinase 1 (CDPK1) is an essential enzyme in the opportunistic pathogen Toxoplasma gondii. CDPK1 controls multiple processes that are essential to the intracellular replicative cycle of T. gondii including secretion of adhesins, motility, invasion, and egress. Remarkably, CDPK1 contains a small glycine gatekeeper residue in the ATP binding pocket making it sensitive to ATP-competitive inhibitors with bulky substituents that complement this expanded binding pocket. Here we explored structure-activity relationships of a series of pyrazolopyrimidine inhibitors of CDPK1 with the goals of increasing selectivity over host enzymes, improving anti-parasite potency, and improving metabolic stability...
September 21, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28933287/modulation-of-abc-transporters-by-nuclear-receptors-physiological-pathological-and-pharmacological-aspects
#2
Juan Pablo Rigalli, Guillermo Nicolás Tocchetti, Johanna Weiss
ABC transporters are membrane proteins mediating the efflux of endo- and xenobiotics. Transporter expression is not static but instead is subject to a dynamic modulation aiming at responding to changes in the internal environment and thus at maintaining homeostatic conditions. Nuclear receptors are ligand modulated transcription factors that get activated upon changes in the intracellular concentrations of the respective agonists and bind to response elements within the promoter of ABC transporters, thus modulating their expression and, consequently, their activity...
September 20, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28932500/effects-of-low-load-resistance-exercise-with-blood-flow-restriction-on-high-energy-phosphate-metabolism-and-oxygenation-level-in-skeletal-muscle
#3
Osamu Yanagisawa, Manabu Sanomura
We aimed to evaluate the effects of low-load resistance exercise with blood flow restriction (BFR) on high-energy phosphate metabolism, intracellular pH, and oxygenation level in the skeletal muscle. Seven males performed low-load ankle plantar flexion exercise (120 repetitions, 30% of one-repetition maximum) with and without BFR (130% of systolic blood pressure) inside a magnetic resonance device. Inorganic phosphate (Pi)-to-phosphocreatine (PCr) ratio, intracellular pH, and tissue oxygenation index (TOI) in the medial gastrocnemius were determined using (31)P-magnetic resonance spectroscopy and near-infrared spectroscopy before and during exercise...
June 2017: Interventional Medicine & Applied Science
https://www.readbyqxmd.com/read/28932199/bacillus-a-biological-tool-for-crop-improvement-through-bio-molecular-changes-in-adverse-environments
#4
REVIEW
Ramalingam Radhakrishnan, Abeer Hashem, Elsayed F Abd Allah
Crop productivity is affected by environmental and genetic factors. Microbes that are beneficial to plants are used to enhance the crop yield and are alternatives to chemical fertilizers and pesticides. Pseudomonas and Bacillus species are the predominant plant growth-promoting bacteria. The spore-forming ability of Bacillus is distinguished from that of Pseudomonas. Members of this genus also survive for a long time under unfavorable environmental conditions. Bacillus spp. secrete several metabolites that trigger plant growth and prevent pathogen infection...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28931870/inactivation-of-hmgcl-promotes-proliferation-and-metastasis-of-nasopharyngeal-carcinoma-by-suppressing-oxidative-stress
#5
Wenqi Luo, Liting Qin, Bo Li, Zhipeng Liao, Jiezhen Liang, Xiling Xiao, Xue Xiao, Yingxi Mo, Guangwu Huang, Zhe Zhang, Xiaoying Zhou, Ping Li
Altered metabolism is considered as a hallmark of cancer. Here we investigated expression of 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) 2 lyase (HMGCL), an essential enzyme in ketogenesis, which produces ketone bodies by the breakdown of fatty acids to supply energy, in nasopharyngeal carcinoma (NPC). The expression of HMGCL was silenced in NPC tissue. Downregulation of HMGCL in NPC was associated with low intracellular β-hydroxybutyrate (β-HB) production, thereby reducing reactive oxygen species (ROS) generation...
September 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28931805/identifying-therapeutic-targets-by-combining-transcriptional-data-with-ordinal-clinical-measurements
#6
Leila Pirhaji, Pamela Milani, Simona Dalin, Brook T Wassie, Denise E Dunn, Robert J Fenster, Julian Avila-Pacheco, Paul Greengard, Clary B Clish, Myriam Heiman, Donald C Lo, Ernest Fraenkel
The immense and growing repositories of transcriptional data may contain critical insights for developing new therapies. Current approaches to mining these data largely rely on binary classifications of disease vs. control, and are not able to incorporate measures of disease severity. We report an analytical approach to integrate ordinal clinical information with transcriptomics. We apply this method to public data for a large cohort of Huntington's disease patients and controls, identifying and prioritizing phenotype-associated genes...
September 20, 2017: Nature Communications
https://www.readbyqxmd.com/read/28931558/pathological-processes-and-therapeutic-advances-in-radioiodide-refractory-thyroid-cancer
#7
Marika H Tesselaar, Jan Wa Smit, James Nagarajah, Romana T Netea-Maier, Theo S Plantinga
Whereas in most patients with non-medullary thyroid cancer (TC) disease remission is achieved by thyroidectomy and ablation of tumor remnants by radioactive iodide (RAI), a substantial subgroup of patients with metastatic disease present tumor lesions that have acquired RAI resistance as a result of dedifferentiation. Although oncogenic mutations in BRAF, TERT promoter and TP53 are associated with an increased propensity for induction of dedifferentiation, the role of genetic and epigenetic aberrations and their effects on important intracellular signaling pathways is not yet fully elucidated...
September 20, 2017: Journal of Molecular Endocrinology
https://www.readbyqxmd.com/read/28930566/homeostatic-regulation-of-plasma-amino-acid-concentrations
#8
Shengfa F Liao, Naresh Regmi, Guoyao Wu
One major goal of nutrition is to maximize the rate of muscle protein gain via provision of amino acids (AAs) through blood plasma. Comparing the plasma AA concentrations with the growth performance data can help to elucidate the metabolic mechanisms regulating plasma AA homeostasis, nutrient utilization, and intracellular protein turnover. Knowledge about the homeostatic regulation of plasma AA profile can aid in predicting dietary AA availabilities, the order of limiting AAs, and the whole body protein metabolism...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28927126/overexpression-and-proliferation-dependence-of-acyl-coa-thioesterase-11-and-13-in-lung-adenocarcinoma
#9
Jen-Yu Hung, Shyh-Ren Chiang, Kuan-Ting Liu, Ming-Ju Tsai, Ming-Shyan Huang, Jiunn-Min Shieh, Meng-Chi Yen, Ya-Ling Hsu
The metabolites of fatty acyl-Coenzyme A (CoA) and metabolic enzymes contribute to lipid biosynthesis, signal transduction, and gene transcription. Previous studies have indicated that elevated concentrations of specific free fatty acids in the plasma and overexpression of specific fatty acyl-CoA metabolic enzymes are observed in patients with lung adenocarcinoma. However, there are >30 enzymes in this metabolic network and have been fully investigated. In the present study, the expression levels of enzymes in the acyl-CoA synthetase (ACS) and acyl-CoA thioesterase (ACOT) families were analyzed from six microarray expression datasets that were collected from Gene Expression Omnibus...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28926758/some-aspects-of-the-iodine-metabolism-of-the-giant-kelp-macrocystis-pyrifera-phaeophyceae
#10
Teresa M Tymon, Eric P Miller, Jennifer L Gonzales, Andrea Raab, Frithjof C Küpper, Carl J Carrano
Despite its paramount role in the functioning of coastal ecosystems, relatively little is known about halogen metabolism in giant kelp (Macrocystis pyrifera). This is an important shortcoming given the potential implications for marine and atmospheric chemical processes in the wide distribution range of Macrocystis. The work presented here constitutes the first in depth investigation of the uptake, efflux, and of the physiological function of iodide in this important kelp species. Iodide uptake and efflux rates were measured in adult sporophytes of Macrocystis under normal and stressed (exogenous hydrogen peroxide and an elicitor-triggered oxidative burst) conditions...
September 8, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28926741/cellular-glutathione-levels-in-hl-60-cells-during-respiratory-burst-are-not-correlated-with-ultra-weak-photon-emission
#11
Rosilene Cristina Rossetto Burgos, Wei Zhang, Eduard P A van Wijk, Thomas Hankemeier, Rawi Ramautar, Jan van der Greef
Recently, ultra-weak photon emission (UPE) was developed as a novel tool for measuring oxidative metabolic processes, as its generation is related to reactive oxygen species (ROS). Both an imbalance in ROS or the uncontrolled production of ROS can lead to oxidative stress, which is commonly associated with many diseases. In addition to playing several biological functions, the thiol amino acid glutathione has an important antioxidant function in the body's defense against ROS. Specifically, glutathione is an important endogenous antioxidant that helps maintain oxidant levels...
September 7, 2017: Journal of Photochemistry and Photobiology. B, Biology
https://www.readbyqxmd.com/read/28926633/effects-of-salinity-on-the-cellular-physiological-responses-of-natrinema-sp-j7-2
#12
Yunjun Mei, Huan Liu, Shunxi Zhang, Ming Yang, Chun Hu, Jian Zhang, Ping Shen, Xiangdong Chen
The halophilic archaea (haloarchaea) live in hyersaline environments such as salt lakes, salt ponds and marine salterns. To cope with the salt stress conditions, haloarchaea have developed two fundamentally different strategies: the "salt-in" strategy and the "compatible-solute" strategy. Although investigation of the molecular mechanisms underlying the tolerance to high salt concentrations has made outstanding achievements, experimental study from the aspect of transcription is rare. In the present study, we monitored cellular physiology of Natrinema sp...
2017: PloS One
https://www.readbyqxmd.com/read/28926236/biofilms-benefiting-plants-exposed-to-zno-and-cuo-nps-studied-with-a-root-mimetic-hollow-fiber-membrane
#13
Michelle Bonebrake, Kaitlyn C Anderson, Jonathan Valiente, Astrid Rosa Jacobson, Joan E McLean, Anne J Anderson, David W Britt
Plants exist with a consortium of microbes that influence plant health, including response to biotic and abiotic stress. While nanoparticle (NP) - plant interactions are increasingly studied, the effect of NPs on the plant microbiome is less researched. Here a root-mimetic hollow fiber membrane (HFM) is presented for generating biofilms of plant-associated microbes nurtured by artificial root exudates (AREs) to correlate exudate composition with biofilm formation and response to NPs. Two microbial isolates from field-grown wheat, a bacillus endophyte and a pseudomonad root surface colonizer, were examined on HFMs fed with AREs varying in N and C composition...
September 19, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28926104/glucose-stimulates-intestinal-epithelial-crypt-proliferation-by-modulating-cellular-energy-metabolism
#14
Weinan Zhou, Deepti Ramachandran, Abdelhak Mansouri, Megan J Dailey
The intestinal epithelium plays an essential role in nutrient absorption, hormone release and barrier function. Maintenance of the epithelium is driven by continuous cell renewal by stem cells located in the intestinal crypts. The amount and type of diet influence this process and result in changes in the size and cellular make-up of the tissue. The mechanism underlying the nutrient-driven changes in proliferation is not known, but may involve a shift in intracellular metabolism that allows for more nutrients to be used to manufacture new cells...
September 19, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28925902/adipose-triglyceride-lipase-regulation-an-overview
#15
Ines Katrin Cerk, Lisa Wechselberger, Monika Oberer
Adipose triglyceride lipase (ATGL) is the key-enzyme for the release of fatty acids (FAs) from triacylglycerol (TG) stores during intracellular lipolysis producing FAs used for energy production. There is growing evidence that the products and intermediates from lipolytic breakdown during the FA mobilization process also have fundamental regulatory functions affecting cell signaling, gene expression, metabolism, cell growth, cell death, and lipotoxicity. Regulation of ATGL is therefore vital for maintaining a defined balance between lipid storage and mobilization...
September 18, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28925901/plant-cell-wall-proteomics-as-a-strategy-to-reveal-candidate-proteins-involved-in-extracellular-lipid-metabolism
#16
Adélaïde Jacq, Vincent Burlat, Elisabeth Jamet
Plant cell walls are composite structures surrounding cells and involved in both mechanical support and perception of their environment. They are mainly composed of polysaccharides (90-95% of their mass) and proteins (5-10%). The cell wall proteins (CWPs) contribute to the arrangements and modifications of polymer networks and to cell-to-cell communication. The structure and composition of cell walls are not uniform in the whole plants, but rather specialized in different cell types to fulfil different functions...
September 18, 2017: Current Protein & Peptide Science
https://www.readbyqxmd.com/read/28924627/structure-and-biogenesis-of-ribonucleoprotein-bodies-in-epidermal-cells-of-caragana-arborescens-l
#17
Elizabeth Kordyum, Ninel Bilyavska
Epidermal cells of leaf petioles, pedicles, and sepals in Caragana arborescens L. are characterized with a unique biogenesis of intracellular bodies, the presence of which continues during 10-12 days in spring, from budding till flowering and fruit inception. Initially, a nuclear body is formed as a derivative of the nucleolus at the beginning of elongation of the protodermal cells, whereas a cytoplasmic body is formed in the proximity of the nuclear envelope later. Nuclear bodies and cytoplasmic bodies do not contain DNA, lipids, and starch, and they consist of RNA tightly packaged with proteins mainly in the form of short thin fibrils with thickness of 6 nm...
September 19, 2017: Protoplasma
https://www.readbyqxmd.com/read/28924233/pharmacological-inhibition-of-camkk2-with-the-selective-antagonist-sto-609-regresses-nafld
#18
Brian York, Feng Li, Fumin Lin, Kathrina L Marcelo, Jianqiang Mao, Adam Dean, Naomi Gonzales, David Gooden, Suman Maity, Cristian Coarfa, Nagireddy Putluri, Anthony R Means
Binding of calcium to its intracellular receptor calmodulin (CaM) activates a family of Ca(2+)/CaM-dependent protein kinases. CaMKK2 (Ca(2+)/CaM-dependent protein kinase kinase 2) is a central member of this kinase family as it controls the actions of a CaMK cascade involving CaMKI, CaMKIV or AMPK. CaMKK2 controls insulin signaling, metabolic homeostasis, inflammation and cancer cell growth highlighting its potential as a therapeutic target for a variety of diseases. STO-609 is a selective, small molecule inhibitor of CaMKK2...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924204/cyclipostins-and-cyclophostin-analogs-as-promising-compounds-in-the-fight-against-tuberculosis
#19
Phuong Chi Nguyen, Vincent Delorme, Anaïs Bénarouche, Benjamin P Martin, Rishi Paudel, Giri R Gnawali, Abdeldjalil Madani, Rémy Puppo, Valérie Landry, Laurent Kremer, Priscille Brodin, Christopher D Spilling, Jean-François Cavalier, Stéphane Canaan
A new class of Cyclophostin and Cyclipostins (CyC) analogs have been investigated against Mycobacterium tuberculosis H37Rv (M. tb) grown either in broth medium or inside macrophages. Our compounds displayed a diversity of action by acting either on extracellular M. tb bacterial growth only, or both intracellularly on infected macrophages as well as extracellularly on bacterial growth with very low toxicity towards host macrophages. Among the eight potential CyCs identified, CyC 17 exhibited the best extracellular antitubercular activity (MIC50 = 500 nM)...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28923861/mct1-inhibitor-azd3965-increases-mitochondrial-metabolism-facilitating-combination-therapy-and-non-invasive-magnetic-resonance-spectroscopy
#20
Mounia Beloueche-Babari, Slawomir Wantuch, Teresa Casals Galobart, Markela Koniordou, Harold G Parkes, Vaitha Arunan, Yuen-Li Chung, Thomas R Eykyn, Paul D Smith, Martin O Leach
Monocarboxylate transporters (MCT) modulate tumor cell metabolism and offer promising therapeutic targets for cancer treatment. Understanding the impact of MCT blockade on tumor cell metabolism may help develop combination strategies or identify pharmacodynamic biomarkers to support the clinical development of MCT inhibitors now in clinical trials. In this study, we assessed the impact of the MCT1 inhibitor AZD3965 on cancer cell metabolism in vitro and in vivo. Exposing human lymphoma and colon carcinoma cells to AZD3965 increased MCT4-dependent accumulation of intracellular lactate, inhibiting monocarboxylate influx and efflux...
September 18, 2017: Cancer Research
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