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https://www.readbyqxmd.com/read/29222162/dual-inhibition-of-pik3c3-and-fgfr-as-a-new-therapeutic-approach-to-treat-bladder-cancer
#1
Chun-Han Chen, C Changou, Tsung-Han Hsieh, Yu-Ching Lee, Cheng-Ying Chu, Kai-Cheng Hsu, Hao-Ching Wang, Yu-Chen Lin, Yan-Ni Lo, Yun-Ru Liu, Jing-Ping Liou, Yun Yen
PURPOSE: MPT0L145 has been developed as a FGFR inhibitor exhibiting significant anti-bladder cancer activity in vitro and in vivo via promoting autophagy-dependent cell death. Here, we aim to elucidate the underlying mechanisms. EXPERIMENTAL DESIGN: Autophagy flux, morphology and intracellular organelles were evaluated by western blotting, transmission electron microscope and fluorescence microscope. Molecular docking, surface plasmon resonance assay were performed to identify drug-protein interaction...
December 8, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29218518/evaluating-the-efficacy-of-glut-inhibitors-using-a-seahorse-extracellular-flux-analyzer
#2
Changyong Wei, Monique Heitmeier, Paul W Hruz, Mala Shanmugam
Glucose is metabolized through anaerobic glycolysis and aerobic oxidative phosphorylation (OXPHOS). Perturbing glucose uptake and its subsequent metabolism can alter both glycolytic and OXPHOS pathways and consequently lactate and/or oxygen consumption. Production and secretion of lactate, as a consequence of glycolysis, leads to acidification of the extracellular medium. Molecular oxygen is the final electron acceptor in the electron transport chain, facilitating oxidative phosphorylation of ADP to ATP. The alterations in extracellular acidification and/or oxygen consumption can thus be used as indirect readouts of glucose metabolism and assessing the impact of inhibiting glucose transport through specific glucose transporters (GLUTs)...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29205089/altered-bioenergetics-profile-in-umbilical-cord-and-amniotic-mesenchymal-stem-cells-from-newborns-of-obese-women
#3
Laura Iaffaldano, Carmela Nardelli, Francesca D'Alessio, Valeria D'Argenio, Marcella Nunziato, Lucia Mauriello, Claudio Procaccini, Giuseppe Maria Maruotti, Pasquale Martinelli, Giuseppe Matarese, Lucio Pastore, Luigi Del Vecchio, Giuseppe Labruna, Lucia Sacchetti
Nutritional imbalance and metabolic alterations associated with maternal obesity during pregnancy predispose offspring to obesity and/or to type 2 diabetes, but the mechanisms underlying these effects are still obscure. In this context, we evaluated whether the two main energy-producing pathways (glycolysis and mitochondrial oxidative phosphorylation) are impaired in obesity during pregnancy thus contributing to metabolic intrauterine alterations. Specifically, we studied metabolic abnormalities in the intrauterine life of newborns using stem cells isolated from amnion and umbilical cord (hA- and hUC-MSCs)...
December 5, 2017: Stem Cells and Development
https://www.readbyqxmd.com/read/29200876/effects-of-insulin-analogs-and-glucagon-like-peptide-1-receptor-agonists-on-proliferation-and-cellular-energy-metabolism-in-papillary-thyroid-cancer
#4
Liang He, Siliang Zhang, Xiaowen Zhang, Rui Liu, Haixia Guan, Hao Zhang
Purpose: This study was aimed to investigate the expressions of the insulin receptor (IR), insulin-like growth factor receptor (IGF-1R), and glucagon-like peptide-1 receptor (GLP-1R) in normal thyroid tissue, papillary thyroid cancer (PTC) tissues, and PTC cells, and to examine the possible role of insulin analogs and GLP-1R agonists in cell proliferation and energy metabolism in PTC cells. Methods: The expressions of IR, IGF-1R, and GLP-1R in PTC tissues and PTC cell lines were detected by immunohistochemistry and western blotting, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29197011/measurement-of-oxidative-stress-mitochondrial-function-using-the-seahorse-system
#5
Dilys T H Leung, Simon Chu
The Seahorse XFp Analyzer is a powerful tool for the assessment of various parameters of cellular respiration. Here we describe the process of the Seahorse Cell Phenotype Test using the Seahorse XFp Analyzer to characterize the metabolic phenotype of live cells. The Seahorse XFp Analyzer can also be coupled with other assays to measure cellular energetics. Given that mitochondrial dysfunction is implicated in preeclampsia, the Seahorse XFp Analyzer will serve as a useful tool for the understanding of pathological metabolism in this disorder...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29180608/t-darpp-activates-igf-1r-signaling-to-regulate-glucose-metabolism-in-trastuzumab-resistant-breast-cancer-cells
#6
Gal Lenz, Angelica Hamilton, Shuhui Geng, Teresa Hong, Markus Kalkum, Jamil Momand, Susan E Kane, Janice Huss
PURPOSE: Increased glycolysis and glucose dependence is a hallmark of malignancy that enables tumors to maximize cell proliferation. In HER2+ cancers, an increase in glycolytic capacity is associated with trastuzumab resistance. IGF-1R activation and t-Darpp over-expression both confer trastuzumab resistance in breast cancer. We therefore investigated a role for IGF-1R and t-Darpp in regulating glycolytic capacity in HER2+ breast cancers. EXPERIMENTAL DESIGN: We examined the relationship between t-Darpp and IGF-1R expression in breast tumors and their respective relationships with patient survival...
November 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29146491/respiratory-stress-in-mitochondrial-electron-transport-chain-complex-mutants-of-candida-albicans-activates-snf1-kinase-response
#7
Pengyi Zhang, Hongbin Li, Jie Cheng, April Y Sun, Liqing Wang, Gordana Mircevska, Richard Calderone, Dongmei Li
We have previously established that mitochondrial Complex I (CI) mutants of Candida albicans display reduced oxygen consumption, decreased ATP production, and increased reactive oxidant species (ROS) during cell growth. Using the Seahorse XF96 analyzer, the energetic phenotypes of Electron Transport Chain (ETC) complex mutants are further characterized in the current study. The underlying regulation of energetic changes in these mutants is determined in glucose and non-glucose conditions when compared to wild type (WT) cells...
November 13, 2017: Fungal Genetics and Biology: FG & B
https://www.readbyqxmd.com/read/29115384/atorvastatin-protects-the-proliferative-ability-of-human-umbilical-vein-endothelial-cells-inhibited-by-angiotensin-ii-by-changing-mitochondrial-energy-metabolism
#8
Ye Chang, Yuan Li, Ning Ye, Xiaofan Guo, Zhao Li, Guozhe Sun, Yingxian Sun
This study aimed to explore whether angiotensin II (Ang II) inhibits the proliferation of human umbilical vein endothelial cells (HUVECs) by changing mitochondrial energy metabolism, and whether atorvastatin has a protective role via restoration of endothelial function. HUVECs were treated with 1 µM Ang II alone or with 10 µM atorvastatin for 24 h. Proliferation was detected by MTT assay, cell counting, 5‑ethynyl‑2'‑deoxyuridine assay and real‑time cell analyzer. Mitochondrial energy metabolism including oxygen consumption rate and extracellular acidification rate were measured using a Seahorse metabolic flux analyzer...
October 19, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29101632/associations-between-microbiota-mitochondrial-function-and-cognition-in-chronic-marijuana-users
#9
Jun Panee, Mariana Gerschenson, Linda Chang
Marijuana (MJ) use is associated with cognitive deficits. Both mitochondrial (mt) dysfunction and gut dysbiosis also affect cognition. We examined whether cognition is related to peripheral blood mononuclear cells' (PBMCs) mt function and fecal microbiota in chronic MJ users. Nineteen chronic MJ users and 20 non-users were evaluated using the Cognition Battery in NIH Toolbox, their mt function for ATP production, and basal and maximal respirations were measured in PBMCs using the Seahorse XFe96 Analyzer, and the abundances of Prevotella and Bacteroides (associated with plant-based and animal product-based diet, respectively) were calculated from stool microbiota analysis...
November 4, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29100178/monitoring-of-reactions-catalyzed-by-lytic-polysaccharide-monooxygenases-using-highly-sensitive-fluorimetric-assay-of-the-oxygen-consumption-rate
#10
Alexander V Gusakov, Alexander G Bulakhov, Ilya N Demin, Arkady P Sinitsyn
Lytic polysaccharide monooxygenases (LPMOs) are recently discovered enzymes that catalyze the oxidative deconstruction of polysaccharides. However fast and reliable methods of determination of LPMO activity still need to be developed, especially those based on the initial reaction rates. A method based on the oxygen consumption rate (OCR) measurements, using a Seahorse XFp Analyzer with highly-sensitive fluorimetric sensors, was applied for monitoring the oxidation of amorphous cellulose by three fungal LPMOs: recombinant enzymes from Thielavia terrestris (GH61E), Trichoderma reesei (Cel61A), and a native LPMO9A from Myceliophthora thermophila...
November 27, 2017: Carbohydrate Research
https://www.readbyqxmd.com/read/29075513/morphology-of-brood-pouch-formation-in-the-pot-bellied-seahorse-hippocampus-abdominalis
#11
Mari Kawaguchi, Ryohei Okubo, Akari Harada, Kazuki Miyasaka, Kensuke Takada, Junya Hiroi, Shigeki Yasumasu
BACKGROUND: The reproductive strategies of vertebrates are diverse. Seahorses (Pisces: Syngnathidae) possess the unique characteristic of male pregnancy; i.e., males, not females, incubate embryos in a specialized structure called a 'brood pouch'. The brood pouch is formed along the ventral midline of the tail. The lumen of the brood pouch is surrounded by loose connective tissue, called pseudoplacenta, and dermis. RESULTS: We visualized and evaluated the morphology of brood pouch formation in Hippocampus abdominalis to gain generalizable insights into this process in seahorses...
2017: Zoological Letters
https://www.readbyqxmd.com/read/29072336/mechanisms-of-toxicity-associated-with-six-tyrosine-kinase-inhibitors-in-human-hepatocyte-cell-lines
#12
Cécile Mingard, Franziska Paech, Jamal Bouitbir, Stephan Krähenbühl
Tyrosine kinase inhibitors have revolutionized the treatment of certain cancers. They are usually well tolerated, but can cause adverse reactions including liver injury. Currently, mechanisms of hepatotoxicity associated with tyrosine kinase inhibitors are only partially clarified. We therefore aimed at investigating the toxicity of regorafenib, sorafenib, ponatinib, crizotinib, dasatinib and pazopanib on HepG2 and partially on HepaRG cells. Regorafenib and sorafenib strongly inhibited oxidative metabolism (measured by the Seahorse-XF24 analyzer) and glycolysis, decreased the mitochondrial membrane potential and induced apoptosis and/or necrosis of HepG2 cells at concentrations similar to steady-state plasma concentrations in humans...
October 26, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/29029014/1-25-dihydroxyvitamin-d-regulation-of-glutamine-synthetase-and-glutamine-metabolism-in-human-mammary-epithelial-cells
#13
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). Here, 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 co-treatment with 1,25D. 1,25D down-regulation of GLUL was sufficient to reduce abundance and activity of GS...
September 28, 2017: Endocrinology
https://www.readbyqxmd.com/read/28987935/in-situ-measurements-of-mitochondrial-matrix-enzyme-activities-using-plasma-and-mitochondrial-membrane-permeabilization-agents
#14
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
https://www.readbyqxmd.com/read/28956099/arsenite-and-methylarsonite-inhibit-mitochondrial-metabolism-and-glucose-stimulated-insulin-secretion-in-ins-1-832-13-%C3%AE-cells
#15
E N Dover, R Beck, M C Huang, C Douillet, Z Wang, E L Klett, Miroslav Stýblo
Growing evidence suggests that exposure to environmental contaminants contributes to the current diabetes epidemic. Inorganic arsenic (iAs), a drinking water and food contaminant, is one of the most widespread environmental diabetogens according to epidemiological studies. Several schemes have been proposed to explain the diabetogenic effects of iAs exposure; however, the exact mechanism remains unknown. We have shown that in vitro exposure to low concentrations of arsenite (iAs(III)) or its trivalent methylated metabolites, methylarsonite (MAs(III)) and dimethylarsinite (DMAs(III)), inhibits glucose-stimulated insulin secretion (GSIS) from isolated pancreatic islets, with little effect on insulin transcription or total insulin content...
September 27, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28942573/berberine-inhibits-oxygen-consumption-rate-independent-of-alteration-in-cardiolipin-levels-in-h9c2-cells
#16
Wenguang Chang, Ming Zhang, Li Chen, Grant M Hatch
Small clinical studies have shown that oral treatment with the plant alkaloid berberine (BBR) reduces blood glucose levels similar to that of metformin and have promoted its use as a novel anti-diabetic therapy. However, in vitro studies have shown that high concentrations of BBR potently inhibit cell proliferation through inhibition of mitochondrial function. Cardiolipin (Ptd2Gro) is a key phospholipid required for regulating mitochondrial bioenergetic function. We examined if BBR inhibited oxygen consumption rate in H9c2 cardiac myocytes through alteration in Ptd2Gro metabolism...
November 2017: Lipids
https://www.readbyqxmd.com/read/28940640/bicarbonate-recycling-by-hif-1-dependent-carbonic-anhydrase-isoforms-9-and-12-is-critical-in-maintaining-intracellular-ph-and-viability-of-nucleus-pulposus-cells
#17
Elizabeth S Silagi, Zachary R Schoepflin, Erin L Seifert, Christophe Merceron, Ernestina Schipani, Irving M Shapiro, Makarand V Risbud
Intervertebral disc degeneration is a ubiquitous condition closely linked to chronic low-back pain. The health of the avascular nucleus pulposus (NP) plays a crucial role in the development of this pathology. We tested the hypothesis that a network comprising HIF-1α, Carbonic anhydrase (CA) 9 and 12 isoforms, and sodium-coupled bicarbonate cotransporters (NBCs) buffer intracellular pH through coordinated bicarbonate recycling. Contrary to the current understanding of NP cell metabolism, analysis of metabolic-flux data from Seahorse XF analyzer showed that CO2 hydration contributes a significant source of extracellular proton production in NP cells, with a smaller input from glycolysis...
September 23, 2017: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28844961/mitochondrial-dysfunction-in-rat-splenocytes-following-hemorrhagic-shock
#18
Marie Warren, Kumar Subramani, Richard Schwartz, Raghavan Raju
The regulation of mitochondrial function is critical in cellular homeostasis following hemorrhagic shock. Hemorrhagic shock results in fluid loss and reduced availability of oxygen and nutrients to tissues. The spleen is a secondary lymphoid organ playing a key role in 'filtering the blood' and in the innate and adaptive immune responses. To understand the molecular basis of hemorrhagic shock, we investigated the changes in splenocyte mitochondrial respiration, and concomitant immune and metabolic alterations...
October 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28844784/dieldrin-induced-neurotoxicity-involves-impaired-mitochondrial-bioenergetics-and-an-endoplasmic-reticulum-stress-response-in-rat-dopaminergic-cells
#19
Jordan T Schmidt, Anna Rushin, Jonna Boyda, Christopher Laurence Souders, Christopher J Martyniuk
Mitochondria are sensitive targets of environmental chemicals. Dieldrin (DLD) is an organochlorine pesticide that remains a human health concern due to high lipid bioaccumulation, and it has been epidemiologically associated to an increased risk for Parkinson's disease (PD). As mitochondrial dysfunction is involved in the etiology of PD, this study aimed to determine whether DLD impaired mitochondrial bioenergetics in dopaminergic cells. Rat immortalized dopaminergic N27 cells were treated for 24 or 48h with one dose of either a solvent control, 2...
August 24, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/28792512/distinct-age-and-differentiation-state-dependent-metabolic-profiles-of-oligodendrocytes-under-optimal-and-stress-conditions
#20
Vijayaraghava T S Rao, Damla Khan, Qiao-Ling Cui, Shih-Chieh Fuh, Shireen Hossain, Guillermina Almazan, Gerhard Multhaup, Luke M Healy, Timothy E Kennedy, Jack P Antel
Within the microenvironment of multiple sclerosis lesions, oligodendrocytes are subject to metabolic stress reflecting effects of focal ischemia and inflammation. Previous studies have shown that under optimal conditions in vitro, the respiratory activity of human adult brain-derived oligodendrocytes is lower and more predominantly glycolytic compared to oligodendrocytes differentiated in vitro from post natal rat brain oligodendrocyte progenitor cells. In response to sub-lethal metabolic stress, adult human oligodendrocytes reduce overall energy production rate impacting the capacity to maintain myelination...
2017: PloS One
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