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https://www.readbyqxmd.com/read/29029014/1-25-dihydroxyvitamin-d-regulation-of-glutamine-synthetase-and-glutamine-metabolism-in-human-mammary-epithelial-cells
#1
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
#2
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
#3
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
#4
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...
September 23, 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
#5
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
#6
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...
August 26, 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
#7
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
#8
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
https://www.readbyqxmd.com/read/28780747/niclosamide-piperazine-prevents-high-fat-diet-induced-obesity-and-diabetic-symptoms-in-mice
#9
Jingjing Guo, Hanlin Tao, Amer Alasadi, Qingrong Huang, Shengkan Jin
PURPOSE: Obesity and type 2 diabetes (T2D) have become the major public health challenges globally. Mitochondrial uncoupling, which reduces intracellular lipid loads and corrects the underlying cause of insulin resistance, has emerged as a promising anti-obese and anti-diabetic intervention. Niclosamide is an anthelmintic drug approved by the US FDA with the mechanism of action that uncouples mitochondria of parasitic worms. Recently, niclosamide ethanolamine salt (NEN) was found to be a safe and effective hepatic mitochondrial uncoupler for the prevention and treatment of obesity and T2D in mouse models...
August 5, 2017: Eating and Weight Disorders: EWD
https://www.readbyqxmd.com/read/28733449/mitochondrial-function-in-engineered-cardiac-tissues-is-co-regulated-by-extracellular-matrix-elasticity-and-tissue-alignment
#10
Davi Marco Lyra-Leite, Allen Mariano Andres, Andrew Patrick Petersen, Nethika Ruvini Ariyasinghe, Nathan Cho, Jezell Athena Lee, Roberta A Gottlieb, Megan L McCain
Mitochondria in cardiac myocytes are critical for generating ATP to meet the high metabolic demands associated with sarcomere shortening. Distinct remodeling of mitochondrial structure and function occur in cardiac myocytes in both developmental and pathological settings. However, the factors that underlie these changes are poorly understood. Because remodeling of tissue architecture and extracellular matrix (ECM) elasticity are also hallmarks of ventricular development and disease, we hypothesize that these environmental factors regulate mitochondrial function in cardiac myocytes...
July 21, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28667285/oxidative-stress-challenge-uncovers-trichloroacetaldehyde-hydrate-induced-mitoplasticity-in-autistic-and-control-lymphoblastoid-cell-lines
#11
Richard Eugene Frye, Shannon Rose, Rebecca Wynne, Sirish C Bennuri, Sarah Blossom, Kathleen M Gilbert, Lynne Heilbrun, Raymond F Palmer
Mitoplasticity occurs when mitochondria adapt to tolerate stressors. Previously we hypothesized that a subset of lymphoblastoid cell lines (LCLs) from children with autistic disorder (AD) show mitoplasticity (AD-A), presumably due to previous environmental exposures; another subset of AD LCLs demonstrated normal mitochondrial activity (AD-N). To better understand mitoplasticity in the AD-A LCLs we examined changes in mitochondrial function using the Seahorse XF96 analyzer in AD and Control LCLs after exposure to trichloroacetaldehyde hydrate (TCAH), an in vivo metabolite of the environmental toxicant and common environmental pollutant trichloroethylene...
June 30, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28611773/fatty-acid-oxidation-compensates-for-lipopolysaccharide-induced-warburg-effect-in-glucose-deprived-monocytes
#12
Nora Raulien, Kathleen Friedrich, Sarah Strobel, Stefan Rubner, Sven Baumann, Martin von Bergen, Antje Körner, Martin Krueger, Manuela Rossol, Ulf Wagner
Monocytes enter sites of microbial or sterile inflammation as the first line of defense of the immune system and initiate pro-inflammatory effector mechanisms. We show that activation with bacterial lipopolysaccharide (LPS) induces them to undergo a metabolic shift toward aerobic glycolysis, similar to the Warburg effect observed in cancer cells. At sites of inflammation, however, glucose concentrations are often drastically decreased, which prompted us to study monocyte function under conditions of glucose deprivation and abrogated Warburg effect...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28600982/altered-bioenergetics-and-enhanced-resistance-to-oxidative-stress-in-human-retinal-pigment-epithelial-cells-from-donors-with-age-related-macular-degeneration
#13
Deborah A Ferrington, Mara C Ebeling, Rebecca J Kapphahn, Marcia R Terluk, Cody R Fisher, Jorge R Polanco, Heidi Roehrich, Michaela M Leary, Zhaohui Geng, James R Dutton, Sandra R Montezuma
Age-related macular degeneration (AMD) is the leading cause of blindness among older adults. It has been suggested that mitochondrial defects in the retinal pigment epithelium (RPE) underlies AMD pathology. To test this idea, we developed primary cultures of RPE to ask whether RPE from donors with AMD differ in their metabolic profile compared with healthy age-matched donors. Analysis of gene expression, protein content, and RPE function showed that these cultured cells replicated many of the cardinal features of RPE in vivo...
June 1, 2017: Redox Biology
https://www.readbyqxmd.com/read/28577850/chronic-myocardial-ischemia-leads-to-loss-of-maximal-oxygen-consumption-and-complex-i-dysfunction
#14
David A Schipper, Ryan Palsma, Katherine M Marsh, Connor O'Hare, Destiny S Dicken, Scott Lick, Toshinobu Kazui, Kitsie Johnson, Ryszard T Smolenski, Dirk J Duncker, Zain Khalpey
BACKGROUND: Cardiomyocytes rely heavily on mitochondrial energy production through oxidative phosphorylation. Chronic myocardial ischemia may cause mitochondrial dysfunction and affect ATP formation. Metabolic changes due to ischemia alters cardiac bioenergetics and hence myocardial function and overall bioenergetic state. Here, we evaluate differences in functional status of respiratory complexes in mitochondrial isolates extracted from left atrial appendage tissue (LAA) from patients undergoing cardiac surgery, with and without chronic ischemia...
October 2017: Annals of Thoracic Surgery
https://www.readbyqxmd.com/read/28577037/metabolic-impact-of-rapamycin-sirolimus-and-b-estradiol-using-mouse-embryonic-fibroblasts-as-a-model-for-lymphangioleiomyomatosis
#15
Katherine M Marsh, David Schipper, Alice S Ferng, Kitsie Johnson, Julia Fisher, Shannon Knapp, Destiny Dicken, Zain Khalpey
INTRODUCTION: Lymphangioleiomyomatosis (LAM) is a rare, progressive cystic lung disease that predominantly affects women of childbearing age. Exogenous rapamycin (sirolimus) has been shown to improve clinical outcomes and was recently approved to treat LAM, whereas estrogen (E2) is implicated in disease progression. No consistent metabolic model currently exists for LAM, therefore wild-type mouse embryonic fibroblasts (MEF +/+) and TSC2 knockout cells (MEF -/-) were used in this study as a model for LAM...
August 2017: Lung
https://www.readbyqxmd.com/read/28545687/synergistic-effect-of-mek-inhibitor-and-metformin-combination-in-low-grade-serous-ovarian-cancer
#16
Ismail Mert, Jasdeep Chhina, Ghassan Allo, Jing Dai, Shelly Seward, Mark S Carey, Marta Llaurado, Shailendra Giri, Ramandeep Rattan, Adnan R Munkarah
OBJECTIVE: Low-grade serous ovarian cancer (LGSOC) constitutes 5-8% of epithelial ovarian cancers and is refractory to chemotherapy. We and others have shown metformin to cause significant growth inhibition in high-grade ovarian cancer both in vitro and in vivo. Here, we aimed to analyze if metformin was effective in inhibiting proliferation of LGSOC alone and in combination with MEK inhibitor. METHODS: Three LGSOC lines (VOA1056, VOA1312 and VOA5646) were treated with metformin, trametinib or 2-deoxyglucose (2DG) alone or in combination with metformin...
August 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28467726/short-communication-hiv-patient-systemic-mitochondrial-respiration-improves-with-exercise
#17
Morgan Kocher, Mindy McDermott, Rachel Lindsey, Cecilia M Shikuma, Mariana Gerschenson, Dominic C Chow, Lindsay B Kohorn, Ronald K Hetzler, Iris F Kimura
In HIV-infected individuals, impaired mitochondrial function may contribute to cardiometabolic disease as well as to fatigue and frailty. Aerobic exercise improves total body energy reserves; however, its impact at the cellular level is unknown. We assessed alterations in cellular bioenergetics in peripheral blood mononuclear cells (PBMC) before and after a 12-week aerobic exercise study in sedentary HIV-infected subjects on stable antiretroviral therapy who successfully completed a 12-week aerobic exercise program...
October 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28447727/advanced-glycation-end-products%C3%A2-induced-mitochondrial-energy-metabolism-dysfunction-alters-proliferation-of-human-umbilical-vein-endothelial-cells
#18
Yuan Li, Ye Chang, Ning Ye, Yintao Chen, Naijin Zhang, Yingxian Sun
Advanced glycation end products (AGEs) restrain the proliferation of endothelial cells, which is an important determinant of diabetic vasculopathy. Mitochondrial biogenesis serves an essential role in cellular adaptation and repair. The current study aimed to investigate alterations in mitochondrial energy metabolism in human umbilical vein endothelial cells (HUVECs) and the latent mechanism regulated by AGEs. The proliferation of cultured HUVECs stimulated with AGEs was detected using an MTT assay and a real‑time cell analyzer (RTCA)...
May 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28438434/connective-tissue-growth-factor-decreases-mitochondrial-metabolism-through-ubiquitin-mediated-degradation-of-mitochondrial-transcription-factor-a-in-oral-squamous-cell-carcinoma
#19
Wei-Ting Lai, Yue-Ju Li, Shi-Bei Wu, Cheng-Ning Yang, Tai-Sheng Wu, Yau-Huei Wei, Yi-Ting Deng
BACKGROUND/PURPOSE: Deregulation of metabolic pathways is one of the hallmarks of cancer progression. Connective tissue growth factor (CTGF/CCN2) acts as a tumor suppressor in oral squamous cell carcinoma (OSCC). However, the role of CTGF in modulating cancer metabolism is still unclear. METHODS: OSCC cells stably overexpressing CTGF (SAS/CTGF) and shRNA against CTGF (TW2.6/shCTGF) were established. Oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) were examined by the Seahorse XF24 analyzer...
April 21, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28435771/brown-adipose-tissue-bioenergetics-a-new-methodological-approach
#20
María Calderon-Dominguez, Martín Alcalá, David Sebastián, Antonio Zorzano, Marta Viana, Dolors Serra, Laura Herrero
The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT...
April 2017: Advanced Science (Weinheim, Baden-Wurttemberg, Germany)
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