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https://www.readbyqxmd.com/read/29691295/metformin-targets-mitochondrial-glycerophosphate-dehydrogenase-mgpdh-to-control-rate-of-oxidative-phosphorylation-and-growth-of-thyroid-cancer-in-vitro-and-in-vivo
#1
Joanna Klubo-Gwiezdzinska, Shilpa Thakur, Brianna Daley, Kelli Gaskins, Vasyl V Vasko, Myriem Boufraqech, Dhaval Patel, Carole Sourbier, Jeff M Reece, Sheue-Yann Cheng, Electron Kebebew, Sunita K Agarwal
PURPOSE: Mitochondrial glycerophosphate dehydrogenase (mGPDH) is the key enzyme connecting oxidative phosphorylation (OXPHOS) and glycolysis as well as a target of the antidiabetic drug metformin (MF) in the liver. There are no data on the expression and role of mGPDH as a metformin target in cancer. In this study, we evaluated mGPDH as a potential target of metformin in thyroid cancer and investigated its contribution in thyroid cancer metabolism. EXPERIMENTAL DESIGN: We analyzed mGPDH expression in 253 thyroid cancer and normal tissues by immunostaining and examined its expression and localization in thyroid cancer-derived cell lines (FTC133, BCPAP) by confocal microscopy...
April 24, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29689339/mitochondrial-dysfunction-is-implicated-in-retinoic-acid-induced-spina-bifida-aperta-in-rat-fetuses
#2
Jia Xue, Hui Gu, Dan Liu, Wei Ma, Xiaowei Wei, Lianshuai Zhao, Yusi Liu, Chaonan Zhang, Zhengwei Yuan
Neural tube defects (NTDs) are the most common and severe congenital malformations, which result from failure of the neural tube to close during embryonic development. The etiology of NTDs is complex, caused by interactions between genetic defects and environmental factors, but the exact mechanisms of this disease are still not fully understood. We herein employ a Seahorse Bioscience microplate-based extracellular flux (XF) analyzer to determine mitochondrial function and quantify respiratory coupling to various bioenergetic functions using specific pharmacological inhibitors of bioenergetic pathways...
April 21, 2018: International Journal of Developmental Neuroscience
https://www.readbyqxmd.com/read/29673597/sennoside-a-protects-mitochondrial-structure-and-function-to-improve-high-fat-diet-induced-hepatic-steatosis-by-targeting-vdac1
#3
Jiamei Le, Weiping Jia, Yongning Sun
Mitochondrial dysfunction is mainly associated with high-fat-diet (HFD)-induced hepatic steatosis. Sennoside A (SA), a commonly used clinical stimulant laxative, is reported to improve energy metabolism and insulin resistance. However, the effect and mechanism of SA on HFD-induced hepatic steatosis remain largely unknown. The aim of this study was to determine the effect and mechanism of SA on HFD-induced hepatic steatosis in mice. We examined the liver and body weight of mice to evaluate the physical changes in the liver...
April 16, 2018: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29649571/spermidine-ameliorates-the-neuronal-aging-by-improving-the-mitochondrial-function-in-vitro
#4
Yu-Hong Jing, Ji-Long Yan, Qing-Jun Wang, Hai-Chao Chen, Xue-Zhu Ma, Jie Yin, Li-Ping Gao
Changes in mitochondrial structure and function are the initial factors of cell aging. Spermidine has an antiaging effect, but its effect on neuronal aging and mitochondrial mechanisms is unclear. In this study, mouse neuroblastoma (N2a) cells were treated with d‑galactose (d‑Gal) to establish cell aging to investigate the antiaging effect and mechanisms of spermidine. Changes in the cell cycle and β-galactosidase activity were analyzed to evaluate the extent of cell aging. Stabilities of mitochondrial mRNA and mitochondrial membrane potential (MMP) were evaluated in the process of cell aging under different treatments...
April 9, 2018: Experimental Gerontology
https://www.readbyqxmd.com/read/29644563/heat-acclimation-increases-mitochondrial-respiration-capacity-of-c2c12-myotubes-and-protects-against-lps-mediated-energy-deficit
#5
Meghan G Patton, Trevor L Gillum, Mandy C Szymanski, Lacey M Gould, Claire J Lauterbach, Roger A Vaughan, Matthew R Kuennen
This work investigated the effect of a 6-day heat acclimation (HA) protocol on myotube metabolic responses at baseline and in response to a subsequent lipopolysaccharide (LPS) challenge. C2C12 myotubes were incubated for 2 h/day at 40 °C for 6 days (HA) or maintained at 37 °C (C). Following 24-h recovery, myotubes were challenged with 500 ng/ml LPS for 2 h, then collected for analysis of protein markers of mitochondrial biogenesis and macronutrient storage. Functional significance of these changes was confirmed with mitochondrial respiration and glycolytic measurements on a Seahorse XF-96 analyzer...
April 11, 2018: Cell Stress & Chaperones
https://www.readbyqxmd.com/read/29644532/methamphetamine-induces-apoptosis-of-microglia-via-the-intrinsic-mitochondrial-dependent-pathway
#6
Anna V Sharikova, Elizabeth Quaye, Jun Yong Park, Maxwell C Maloney, Habben Desta, Ramkumar Thiyagarajan, Kenneth L Seldeen, Neil U Parikh, Parteet Sandhu, Alexander Khmaladze, Bruce R Troen, Stanley A Schwartz, Supriya D Mahajan
Methamphetamine (METH) is a drug of abuse, the acute and chronic use of which induces neurotoxic responses in the human brain, ultimately leading to neurocognitive disorders. Our goals were to understand the impact of METH on microglial mitochondrial respiration and to determine whether METH induces the activation of the mitochondrial-dependent intrinsic apoptosis pathway in microglia. We assessed the expression of pro- apoptosis genes using qPCR of RNA extracted from a human microglial cell line (HTHU). We examined the apoptosis-inducing effects of METH on microglial cells using digital holographic microscopy (DHM) to quantify real-time apoptotic volume decrease (AVD) in microglia in a noninvasive manner...
April 11, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29618935/metabolic-profiling-of-follistatin-overexpression-a-novel-therapeutic-strategy-for-metabolic-diseases
#7
Rajan Singh, Shehla Pervin, Se-Jin Lee, Alan Kuo, Victor Grijalva, John David, Laurent Vergnes, Srinivasa T Reddy
Background: Follistatin (Fst) promotes brown adipocyte characteristics in adipose tissues. Methods: Abdominal fat volume (CT scan), glucose clearance (GTT test), and metabolomics analysis (mass spectrometry) of adipose tissues from Fst transgenic (Fst-Tg) and wild type (WT) control mice were analyzed. Oxygen consumption (Seahorse Analyzer) and lipidomics (gas chromatography) was analyzed in 3T3-L1 cells. Results: Fst-Tg mice show significant decrease in abdominal fat content, increased glucose clearance, improved plasma lipid profiles and significant changes in several conventional metabolites compared to the WT mice...
2018: Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy
https://www.readbyqxmd.com/read/29618839/metformin-adapts-its-cellular-effects-to-bioenergetic-status-in-a-model-of-metabolic-dysfunction
#8
Christopher Auger, Thibacg Sivayoganathan, Abdikarim Abdullahi, Alexandra Parousis, Bo Wen Pang, Marc G Jeschke
Thermal injury induces a complex immunometabolic response, characterized by hyperglycemia, extensive inflammation and persistent hypermetabolism. It has been suggested that attenuation of the hypermetabolic response is beneficial for patient wellbeing. To that effect, metformin represents an attractive therapeutic agent, as its effects on glycemia, inflammation and bioenergetics can improve outcomes in burn patients. Therefore, we studied metformin and its effects on mitochondrial bioenergetics in a murine model of thermal injury...
April 4, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29615095/loss-of-xbp1-accelerates-age-related-decline-in-retinal-function-and-neurodegeneration
#9
Todd McLaughlin, Marek Falkowski, Jae Whan Park, Stephen Keegan, Michael Elliott, Joshua J Wang, Sarah X Zhang
BACKGROUND: Aging is the strongest risk factor for neurodegenerative diseases and extended age results in neuronal degeneration and functional decline in the visual system. Among many contributing factors to age-related deterioration of neurons is an insufficient activation of the Unfolded Protein Response (UPR) in the endoplasmic reticulum (ER) in response to cellular stress. X-box binding protein 1 (XBP1) is a major component of the UPR and is essential for maintaining protein homeostasis and reducing cellular stresses...
April 4, 2018: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/29613828/activation-of-class-i-histone-deacetylases-contributes-to-mitochondrial-dysfunction-in-cardiomyocytes-with-altered-complex-activities
#10
Baigalmaa Lkhagva, Yu-Hsun Kao, Ting-I Lee, Ting-Wei Lee, Wan-Li Cheng, Yi-Jen Chen
Histone deacetylases (HDACs) play vital roles in the pathophysiology of heart failure, which is associated with mitochondrial dysfunction. Tumor necrosis factor-α (TNF-α) contributes to the genesis of heart failure and impairs mitochondria. This study evaluated the role of HDACs in TNF-α-induced mitochondrial dysfunction and investigated their therapeutic potential and underlying mechanisms. We measured mitochondrial oxygen consumption rate (OCR) and ATP production using Seahorse XF24 extracellular flux analyzer and bioluminescent assay in control and TNF-α (10 ng/ml, 24 h)-treated HL-1 cells with or without HDAC inhibition...
April 3, 2018: Epigenetics: Official Journal of the DNA Methylation Society
https://www.readbyqxmd.com/read/29594127/effect-of-eicosapentaenoic-acid-and-docosahexaenoic-acid-on-myogenesis-and-mitochondrial-biosynthesis-during-murine-skeletal-muscle-cell-differentiation
#11
Tun-Yun Hsueh, Jamie I Baum, Yan Huang
Polyunsaturated fatty acids are important nutrients for human health, especially omega-3 fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which have been found to play positive roles in the prevention of various diseases. However, previous studies have reported that excessive omega-3 fatty acids supplement during pregnancy caused side effects such as slower neural transmission times and postnatal growth restriction. In this study, we investigated the effect of EPA and DHA on mitochondrial function and gene expression in C2C12 myoblasts during skeletal muscle differentiation...
2018: Frontiers in Nutrition
https://www.readbyqxmd.com/read/29550120/%C3%AE-lactalbumin-oleic-acid-complex-kills-tumor-cells-by-inducing-excess-energy-metabolism-but-inhibiting-mrna-expression-of-the-related-enzymes
#12
B Fang, M Zhang, K S Ge, H Z Xing, F Z Ren
Previous studies have demonstrated that the anti-tumor α-lactalbumin-oleic acid complex (α-LA-OA) may target the glycolysis of tumor cells. However, few data are available regarding the effects of α-LA-OA on energy metabolism. In this study, we measured glycolysis and mitochondrial functions in HeLa cells in response to α-LA-OA using the XF flux analyzer (Seahorse Bioscience, North Billerica, MA). The gene expression of enzymes involved in glycolysis, tricarboxylic acid cycle, electron transfer chain, and ATP synthesis were also evaluated...
March 14, 2018: Journal of Dairy Science
https://www.readbyqxmd.com/read/29503646/pentose-phosphate-shunt-modulates-reactive-oxygen-species-and-nitric-oxide-production-controlling-trypanosoma-cruzi-in-macrophages
#13
Sue-Jie Koo, Bartosz Szczesny, Xianxiu Wan, Nagireddy Putluri, Nisha Jain Garg
Metabolism provides substrates for reactive oxygen species (ROS) and nitric oxide (NO) generation, which are a part of the macrophage (Mφ) anti-microbial response. Mφs infected with Trypanosoma cruzi ( Tc ) produce insufficient levels of oxidative species and lower levels of glycolysis compared to classical Mφs. How Mφs fail to elicit a potent ROS/NO response during infection and its link to glycolysis is unknown. Herein, we evaluated for ROS, NO, and cytokine production in the presence of metabolic modulators of glycolysis and the Krebs cycle...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29484415/metformin-facilitates-bg45%C3%A2-induced-apoptosis-via-an-anti%C3%A2-warburg-effect-in-cholangiocarcinoma-cells
#14
Dehua Tang, Lei Xu, Mingming Zhang, Robert Gregory Dorfman, Yida Pan, Qian Zhou, Lixing Zhou, Yuming Wang, Yang Li, Yuyao Yin, Lei Wang, Xiaoping Zou
Cholangiocarcinoma (CCA) is a highly lethal malignancy with an often late diagnosis and consequent poor prognosis. Chemotherapy is the only therapeutic strategy for most patients. Compared to normal cells, tumor cells preferentially metabolize glucose to lactate, even in aerobic conditions. Such metabolic alterations not only support the growth and invasion of tumor cells, but also promote their chemoresistance. The purpose of our study was to explore the role of metformin in regulating the metabolism of CCA, as well as to investigate whether metformin could act as a chemosensitizer of the HDAC3 inhibitor BG45, and therefore have potential for the treatment of CCA...
February 20, 2018: Oncology Reports
https://www.readbyqxmd.com/read/29480483/study-of-ampk-regulated-metabolic-fluxes-in-neurons-using-the-seahorse-xfe-analyzer
#15
Claudia Marinangeli, Jérome Kluza, Philippe Marchetti, Luc Buée, Valérie Vingtdeux
AMP-activated protein kinase (AMPK) is the intracellular master energy sensor and metabolic regulator. AMPK is involved in cell energy homeostasis through the regulation of glycolytic flux and mitochondrial biogenesis. Interestingly, metabolic dysfunctions and AMPK deregulations are observed in many neurodegenerative diseases, including Alzheimer's. While these deregulations could play a key role in the development of these diseases, the study of metabolic fluxes has remained quite challenging and time-consuming...
2018: Methods in Molecular Biology
https://www.readbyqxmd.com/read/29466249/exploiting-mitochondrial-targeting-signal-s-tpp-and-bis-tpp-for-eradicating-cancer-stem-cells-cscs
#16
Bela Ozsvari, Federica Sotgia, Michael P Lisanti
Tri-phenyl-phosphonium (TPP) is a non-toxic chemical moiety that functionally behaves as a mitochondrial targeting signal (MTS) in living cells. Here, we explored the hypothesis that TPP-related compounds could be utilized to inhibit mitochondria in cancer stem cells (CSCs). We randomly selected 9 TPP-related compounds for screening, using an ATP depletion assay. Based on this approach, five compounds were identified as "positive hits"; two had no detectable effect on ATP production. Remarkably, this represents a >50% hit rate...
February 19, 2018: Aging
https://www.readbyqxmd.com/read/29431119/hypermetabolic-macrophages-in-rheumatoid-arthritis-and-coronary-artery-disease-due-to-glycogen-synthase-kinase-3b-inactivation
#17
Markus Zeisbrich, Rolando E Yanes, Hui Zhang, Ryu Watanabe, Yinyin Li, Lukas Brosig, Jison Hong, Barbara B Wallis, John C Giacomini, Themistocles L Assimes, Jörg J Goronzy, Cornelia M Weyand
OBJECTIVES: Accelerated atherosclerotic disease typically complicates rheumatoid arthritis (RA), leading to premature cardiovascular death. Inflammatory macrophages are key effector cells in both rheumatoid synovitis and the plaques of coronary artery disease (CAD). Whether both diseases share macrophage-dependent pathogenic mechanisms is unknown. METHODS: Patients with RA or CAD (at least one myocardial infarction) and healthy age-matched controls were recruited into the study...
February 3, 2018: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29391024/chi3l3-a-potential-key-orchestrator-of-eosinophil-recruitment-in-meningitis-induced-by-angiostrongylus-cantonensis
#18
Shuo Wan, Xiaoqiang Sun, Feng Wu, Zilong Yu, Lifu Wang, Datao Lin, Zhengyu Li, Zhongdao Wu, Xi Sun
BACKGROUND: Angiostrongylus cantonensis, an important foodborne parasite, can induce serious eosinophilic meningitis in non-permissive hosts, such as mouse and human. However, the characteristics and mechanisms of the infection are still poorly understood. This study sought to determine the key molecules and its underlying mechanism in inducing brain eosinophilic infiltration caused by Angiostrongylus cantonensis. METHODS: Mathematical models were established for prediction of significantly changing genes and the functional associated protein with RNA-seq data in Angiostrongylus cantonensis infection...
February 2, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29389743/mice-overexpressing-chromogranin-a-display-hypergranulogenic-adrenal-glands-with-attenuated-atp-levels-contributing-to-the-hypertensive-phenotype
#19
Saiful A Mir, Ying Li, Jacob D Story, Soma Bal, Linda Awdishu, Anneke A Street, Ravindra L Mehta, Prabhleen Singh, Sucheta M Vaingankar
OBJECTIVE: Elevated circulating chromogranin A (CHGA) is observed in human hypertension. CHGA is critical for granulogenesis and exocytosis of catecholamine stores from secretory large dense core vesicles (LDCV). This study aims to understand the morphological, molecular and phenotypic changes because of excess CHGA and the mechanistic link eventuating in hyper-adrenergic hypertension. METHODS: Blood pressure and heart rate was monitored in mouse models expressing normal and elevated level of CHGA by telemetry...
January 31, 2018: Journal of Hypertension
https://www.readbyqxmd.com/read/29380243/quercetin-exerts-an-inhibitory-effect-on-cellular-bioenergetics-of-the-b164a5-murine-melanoma-cell-line
#20
Adrian Sturza, Ioana Pavel, Sebastian Ancușa, Corina Danciu, Cristina Dehelean, Oana Duicu, Danina Muntean
Modulation of mitochondrial bioenergetics and glycolysis in malignancies has recently emerged a potential chemotherapeutic strategy since numerous malignant cells have overcome inhibition of the glycolytic pathway by increasing mitochondrial ATP production. Quercetin is a flavonoid with antioxidant, antiangiogenic, and chemoprotective properties but the mitochondrial effects are less characterized. The present study was purported to assess the effects of quercetin on the bioenergetic profile of B164A5 murine melanoma cell line...
January 29, 2018: Molecular and Cellular Biochemistry
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