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https://www.readbyqxmd.com/read/28792512/distinct-age-and-differentiation-state-dependent-metabolic-profiles-of-oligodendrocytes-under-optimal-and-stress-conditions
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
June 1, 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
#8
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
#9
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/hiv-patient-systemic-mitochondrial-respiration-improves-with-exercise
#10
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...
June 20, 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
#11
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
#12
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
#13
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)
https://www.readbyqxmd.com/read/28359291/curcumin-suppresses-gastric-tumor-cell-growth-via-ros-mediated-dna-polymerase-%C3%AE-depletion-disrupting-cellular-bioenergetics
#14
Lihua Wang, Xiwen Chen, Zhuanyun Du, Gefei Li, Mayun Chen, Xi Chen, Guang Liang, Tongke Chen
BACKGROUND: Curcumin, as a pro-apoptotic agent, is extensively studied to inhibit tumor cell growth of various tumor types. Previous work has demonstrated that curcumin inhibits cancer cell growth by targeting multiple signaling transduction and cellular processes. However, the role of curcumin in regulating cellular bioenergetic processes remains largely unknown. METHODS: Western blotting and qRT-PCR were performed to analyze the protein and mRNA level of indicated molecules, respectively...
March 31, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28276032/identification-of-disease-causing-mutations-by-functional-complementation-of-patient-derived-fibroblast-cell-lines
#15
Laura S Kremer, Holger Prokisch
Diagnosis of mitochondrial disorders is still hampered by their phenotypic and genotypic heterogeneity. In many cases, exome sequencing, the state-of-the-art method for genetically diagnosing mitochondrial disease patients, does not allow direct identification of the disease-associated gene but rather results in a list of variants in candidate genes. Here, we present a method to validate the disease-causing variant based on functional complementation assays. First, cell lines expressing a wild-type cDNA of the candidate genes are generated by lentiviral infection of patient-derived fibroblasts...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28276021/assessing-mitochondrial-bioenergetics-in-isolated-mitochondria-from-various-mouse-tissues-using-seahorse-xf96-analyzer
#16
Arcangela Iuso, Birgit Repp, Caroline Biagosch, Caterina Terrile, Holger Prokisch
Working with isolated mitochondria is the gold standard approach to investigate the function of the electron transport chain in tissues, free from the influence of other cellular factors. In this chapter, we outline a detailed protocol to measure the rate of oxygen consumption (OCR) with the high-throughput analyzer Seahorse XF96. More importantly, this protocol wants to provide practical tips for handling many different samples at once, and take a real advantage of using a high-throughput system. As a proof of concept, we have isolated mitochondria from brain, heart, liver, muscle, kidney, and lung of a wild-type mouse, and measured basal respiration (State II), ADP-stimulated respiration (State III), non-ADP-stimulated respiration (State IVo), and FCCP-stimulated respiration (State IIIu) using respiratory substrates specific to the respiratory chain complex I (RCCI) and complex II (RCCII)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28245898/glutamate-impairs-mitochondria-aerobic-respiration-capacity-and-enhances-glycolysis-in-cultured-rat-astrocytes
#17
Xu Yan, Zhong Fang Shi, Li Xin Xu, Jia Xin Li, Min Wu, Xiao Xuan Wang, Mei Jia, Li Ping Dong, Shao Hua Yang, Fang Yuan
OBJECTIVE: To study the effect of glutamate on metabolism, shifts in glycolysis and lactate release in rat astrocytes. METHODS: After 10 days, secondary cultured astrocytes were treated with 1 mmol/L glutamate for 1 h, and the oxygen consumption rates (OCR) and extra cellular acidification rate (ECAR) was analyzed using a Seahorse XF 24 Extracellular Flux Analyzer. Cell viability was then evaluated by MTT assay. Moreover, changes in extracellular lactate concentration induced by glutamate were tested with a lactate detection kit...
January 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28237843/characterization-of-energy-and-neurotransmitter-metabolism-in-cortical-glutamatergic-neurons-derived-from-human-induced-pluripotent-stem-cells-a-novel-approach-to-study-metabolism-in-human-neurons
#18
Blanca I Aldana, Yu Zhang, Maria Fog Lihme, Lasse K Bak, Jørgen E Nielsen, Bjørn Holst, Poul Hyttel, Kristine K Freude, Helle S Waagepetersen
Alterations in the cellular metabolic machinery of the brain are associated with neurodegenerative disorders such as Alzheimer's disease. Novel human cellular disease models are essential in order to study underlying disease mechanisms. In the present study, we characterized major metabolic pathways in neurons derived from human induced pluripotent stem cells (hiPSC). With this aim, cultures of hiPSC-derived neurons were incubated with [U-(13)C]glucose, [U-(13)C]glutamate or [U-(13)C]glutamine. Isotopic labeling in metabolites was determined using gas chromatography coupled to mass spectrometry, and cellular amino acid content was quantified by high-performance liquid chromatography...
June 2017: Neurochemistry International
https://www.readbyqxmd.com/read/28197868/plasma-levels-of-immune-factors-and-sex-steroids-in-the-male-seahorse-hippocampus-erectus-during-a-breeding-cycle
#19
Tingting Lin, Xin Liu, Dongxue Xiao, Dong Zhang
To better understand the endocrine- and immune-response pattern during reproduction in a fish species having parental care behaviors and also to accumulate the endocrine- and immune-related data for future explanations of the low reproductive efficiency in seahorse species, the variations of immune factors and sex steroids in the plasma of the male lined seahorse Hippocampus erectus at different breeding stages, i.e., pre-pregnancy, pregnancy (early, middle, and late periods), and post-pregnancy, were investigated in the present study...
June 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28179998/phlpp-regulates-hexokinase-2-dependent-glucose-metabolism-in-colon-cancer-cells
#20
Xiaopeng Xiong, Yang-An Wen, Mihail I Mitov, Mary C Oaks, Shigeki Miyamoto, Tianyan Gao
Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect...
2017: Cell Death Discovery
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