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https://www.readbyqxmd.com/read/28545687/synergistic-effect-of-mek-inhibitor-and-metformin-combination-in-low-grade-serous-ovarian-cancer
#1
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...
May 22, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/28467726/hiv-patient-systemic-mitochondrial-respiration-improves-with-exercise
#2
Morgan Kocher, Mindy McDermott, Rachel Lindsey, Cecilia Shikuma, Mariana Gerschenson, Dominic Chow, Lindsay Kohorn, Ronald K Hetzler, Iris Kimura
INTRODUCTION: In HIV-infected individuals, impaired mitochondrial function may contribute to cardio-metabolic 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 (ART) who successfully completed a 12 week aerobic exercise program...
May 3, 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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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...
February 24, 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
#11
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
#12
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
https://www.readbyqxmd.com/read/28110213/cannabidiol-attenuates-ogd-r-induced-damage-by-enhancing-mitochondrial-bioenergetics-and-modulating-glucose-metabolism-via-pentose-phosphate-pathway-in-hippocampal-neurons
#13
Shanshan Sun, Fangyuan Hu, Jihong Wu, Shenghai Zhang
Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen-glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/28047565/su-g-tep3-10-radiation-induces-prompt-live-cell-metabolic-fluxes
#14
D Campos, W Peeters, K Nickel, B Burkel, J Bussink, R Kimple, A van der Kogel, K Eliceiri, M Kissick
PURPOSE: To compare metabolic dynamics and HIF-1α expression following radiation between a cancerous cell line (UM-SCC-22B) and a normal, immortalized cell line, NOK (Normal Oral Keratinocyte). HIF-1 is a key factor in metabolism and radiosensitivity. A better understanding of how radiation affects the interplay of metabolism and HIF-1 might give a better understanding of the mechanisms responsible for radiosensitivity. METHODS: Changes in cellular metabolism in response to radiation are tracked by fluorescence lifetime of NADH...
June 2016: Medical Physics
https://www.readbyqxmd.com/read/28006775/fgf-2-transcriptionally-down-regulates-the-expression-of-bnip3l-via-pi3k-akt-foxo3a-signaling-and-inhibits-necrosis-and-mitochondrial-dysfunction-induced-by-high-concentrations-of-hydrogen-peroxide-in-h9c2-cells
#15
Qian Chen, Xiaosong Chen, Conghui Han, Ying Wang, Tao Huang, Yingdong Du, Zhen Dong
BACKGROUND/AIMS: Cardiovascular disease is a growing major global public health problem. Necrosis is one of the main forms of cardiomyocyte death in heart disease. Oxidative stress is regarded as one of the key regulators of cardiac necrosis, which eventually leads to cardiovascular disease. Many pharmacological and in vitro studies have suggested that FGF-2 can act directly on cardiomyocytes to maintain the integrity and function of the myocardium and prevent damage during oxidative stress...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27997810/glucose-transporter-1-dependent-glycolysis-is-increased-during-aging-related-lung-fibrosis-and-phloretin-inhibits-lung-fibrosis
#16
Soo Jung Cho, Jong-Seok Moon, Chang-Min Lee, Augustine M K Choi, Heather W Stout-Delgado
Aging is associated with metabolic diseases such as type 2 diabetes mellitus, cardiovascular disease, cancer, and neurodegeneration. Aging contributes to common processes including metabolic dysfunction, DNA damage, and reactive oxygen species generation. Although glycolysis has been linked to cell growth and proliferation, the mechanisms by which the activation of glycolysis by aging regulates fibrogenesis in the lung remain unclear. The objective of this study was to determine if glucose transporter 1 (GLUT1)-induced glycolysis regulates age-dependent fibrogenesis of the lung...
April 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/27889640/inhibition-of-autophagy-with-bafilomycin-and-chloroquine-decreases-mitochondrial-quality-and-bioenergetic-function-in-primary-neurons
#17
Matthew Redmann, Gloria A Benavides, Taylor F Berryhill, Willayat Y Wani, Xiaosen Ouyang, Michelle S Johnson, Saranya Ravi, Stephen Barnes, Victor M Darley-Usmar, Jianhua Zhang
Autophagy is an important cell recycling program responsible for the clearance of damaged or long-lived proteins and organelles. Pharmacological modulators of this pathway have been extensively utilized in a wide range of basic research and pre-clinical studies. Bafilomycin A1 and chloroquine are commonly used compounds that inhibit autophagy by targeting the lysosomes but through distinct mechanisms. Since it is now clear that mitochondrial quality control, particularly in neurons, is dependent on autophagy, it is important to determine whether these compounds modify cellular bioenergetics...
April 2017: Redox Biology
https://www.readbyqxmd.com/read/27872984/cinnamic-acid-derivatives-enhance-the-efficacy-of-transarterial-embolization-in-a-rat-model-of-hepatocellular-carcinoma
#18
Luke R Wilkins, David L Brautigan, Hanping Wu, Hooman Yarmohammadi, Ewa Kubicka, Vlad Serbulea, Norbert Leitinger, Wendy Liu, John R Haaga
INTRODUCTION: We hypothesize that the combination of transarterial embolization (TAE) plus inhibition of lactate export will limit anaerobic metabolism and reduce tumor survival compared to TAE alone. The purpose of this study was to test this hypothesis in a rat model of hepatocellular carcinoma (HCC). METHODS: Rat N1-S1 hepatoma cells were assayed in vitro using the Seahorse XF analyzer to measure extracellular acidification (lactate excretion) comparing effects of the addition of caffeic acid (CA) or ferulic acid (FA) or UK-5099 with control...
March 2017: Cardiovascular and Interventional Radiology
https://www.readbyqxmd.com/read/27791989/stimulation-of-the-toll-like-receptor-3-promotes-metabolic-reprogramming-in-head-and-neck-carcinoma-cells
#19
Mathieu Veyrat, Sylvère Durand, Marion Classe, Tanja Matijevic Glavan, Natalie Oker, Nikiforos-Ioannis Kapetanakis, Xiaojun Jiang, Aurore Gelin, Philippe Herman, Odile Casiraghi, David Zagzag, David Enot, Pierre Busson, Benjamin Vérillaud
In this study, a possible link between the innate immune recognition receptor TLR3 and metabolic reprogramming in Head and Neck carcinoma (HNC) cells was investigated. The effects of TLR3 stimulation/knock-down were assessed under several culture conditions in 4 HNC cell-lines by cell growth assays, targeted metabolomics, and glycolysis assays based on time-resolved analysis of proton release (Seahorse analyzer). The stimulation of TLR3 by its synthetic agonist Poly(A:U) resulted in a faster growth of HNC cells under low foetal calf serum conditions...
December 13, 2016: Oncotarget
https://www.readbyqxmd.com/read/27784195/mitochondrial-spare-respiratory-capacity-is-negatively-correlated-with-nuclear-reprogramming-efficiency
#20
Yan Zhou, Rasha Abdelkadhem Al-Saaidi, Paula Fernandez-Guerra, Kristine K Freude, Rikke Katrine Jentoft Olsen, Uffe Birk Jensen, Niels Gregersen, Poul Hyttel, Lars Bolund, Lars Aagaard, Peter Bross, Yonglun Luo
Nuclear reprogramming efficiency has been shown to be highly variable among different types of somatic cells and different individuals, yet the underlying mechanism remains largely unknown. Several studies have shown that reprogramming of fibroblasts into induced pluripotent stem cells (iPSCs) requires remodeling of mitochondria and a metabolic shift from an oxidative state to a more glycolytic state. In this study, we evaluated the nuclear reprogramming efficiency in relation to mitochondrial bioenergetic parameters of fibroblasts from seven different human individuals...
February 1, 2017: Stem Cells and Development
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