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https://www.readbyqxmd.com/read/28176017/hypoxia-and-aerobic-metabolism-adaptations-of-human-endothelial-cells
#1
Agnieszka Koziel, Wieslawa Jarmuszkiewicz
The goal of our study was to assess the influence of chronic exposure to hypoxia on mitochondrial oxidative metabolism in human umbilical vein endothelial cells (EA.hy926 line) cultured for 6 days at 1% O2 tension. The hypoxia-induced effects were elucidated at the cellular and isolated mitochondria levels. Hypoxia elevated fermentation but did not change mitochondrial biogenesis or the aerobic respiratory capacity of endothelial cells. In endothelial cells, hypoxia caused a general decrease in mitochondrial respiration during carbohydrate, fatty acid, and amino acid oxidation but increased exclusively ketogenic amino acid oxidation...
February 8, 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28143904/ampk-promotes-mitochondrial-biogenesis-and-function-by-phosphorylating-the-epigenetic-factors-dnmt1-rbbp7-and-hat1
#2
Traci L Marin, Brendan Gongol, Fan Zhang, Marcy Martin, David A Johnson, Han Xiao, Yinsheng Wang, Shankar Subramaniam, Shu Chien, John Y-J Shyy
Adenosine monophosphate (AMP)-activated protein kinase (AMPK) acts as a master regulator of cellular energy homeostasis by directly phosphorylating metabolic enzymes and nutrient transporters and by indirectly promoting the transactivation of nuclear genes involved in mitochondrial biogenesis and function. We explored the mechanism of AMPK-mediated induction of gene expression. We identified AMPK consensus phosphorylation sequences in three proteins involved in nucleosome remodeling: DNA methyltransferase 1 (DNMT1), retinoblastoma binding protein 7 (RBBP7), and histone acetyltransferase 1 (HAT1)...
January 31, 2017: Science Signaling
https://www.readbyqxmd.com/read/28130201/ucp2-up-regulation-within-the-course-of-autoimmune-encephalomyelitis-correlates-with-t-lymphocyte-activation
#3
Alina Smorodchenko, Stephanie Schneider, Anne Rupprecht, Karoline Hilse, Soleman Sasgary, Ute Zeitz, Reinhold G Erben, Elena E Pohl
Multiple sclerosis (MS) is an inflammatory demyelinating autoimmune disorder of the central nervous system (CNS) associated with severe neurological disability. Reactive oxygen species (ROS) and mitochondrial dysfunction play a pivotal role in the pathogenesis of this disease. Several members of the mitochondrial uncoupling protein subfamily (UCP2-UCP5) were suggested to regulate ROS by diminishing the mitochondrial membrane potential and constitute therefore a promising pharmacological target for MS. To evaluate the role of different uncoupling proteins in neuroinflammation, we have investigated their expression patterns in murine brain and spinal cord (SC) during different stages of experimental autoimmune encephalomyelitis (EAE), an animal model for MS...
January 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28130074/loss-of-ucp2-impairs-cold-induced-non-shivering-thermogenesis-by-promoting-a-shift-toward-glucose-utilization-in-brown-adipose-tissue
#4
Alexandre Caron, Sébastien M Labbé, Sophie Carter, Marie-Claude Roy, Roger Lecomte, Daniel Ricquier, Frédéric Picard, Denis Richard
Uncoupling protein 2 (UCP2) was discovered in 1997 and classified as an uncoupling protein largely based on its homology of sequence with UCP1. Since its discovery, the uncoupling function of UCP2 has been questioned and there is yet no consensus on the true function of this protein. UCP2 was first proposed to be a reactive oxygen species (ROS) regulator and an insulin secretion modulator. More recently, it was demonstrated as a regulator of the mitochondrial fatty acid oxidation, which prompted us to investigate its role in the metabolic and thermogenic functions of brown adipose tissue...
March 2017: Biochimie
https://www.readbyqxmd.com/read/28104982/mirna-133a-ucp2-pathway-regulates-inflammatory-bowel-disease-progress-by-influencing-inflammation-oxidative-stress-and-energy-metabolism
#5
Xi Jin, Dong Chen, Ruo-Heng Zheng, Hong Zhang, Yi-Peng Chen, Zun Xiang
AIM: To investigate the role of the miR-133a-UCP2 pathway in the pathogenesis of inflammatory bowel disease (IBD) and to explore the potential downstream mechanisms with respect to inflammation, oxidative stress and energy metabolism. METHODS: C57BL/6 mice were fed dextran sulfate sodium (DSS) liquid for 7 consecutive days, followed by the administration of saline to the DSS group, UCP2 siRNA to the UCP2 group and a miR-133a mimic to the miR-133a group on days 8 and 11...
January 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28089824/mitochondrial-uncoupling-protein-2-in-human-cumulus-cells-is-associated-with-regulating-autophagy-and-apoptosis-maintaining-gap-junction-integrity-and-progesterone-synthesis
#6
Hongshan Ge, Fan Zhang, Ping Duan, Nan Zhu, Jiayan Zhang, Feijun Ye, Dan Shan, Hua Chen, XiaoSheng Lu, ChunFang Zhu, Renshan Ge, Zhenkun Lin
To explore the roles of mitochondrial Uncoupling Protein 2 (UCP2) in cumulus cells (CCs), human CCs were cultured in vitro, and the UCP2 was inhibited by treatment with Genipin, a special UCP inhibitor, or by RNA interference targeting UCP2. No significant differences in adenosine triphosphate levels and the ratio of ADP/ATP were observed after UCP2 inhibition. UCP2 inhibition caused a significant increase in cellular oxidative damage, which was reflected in alterations to several key parameters, including reactive oxygen species (ROS) and lipid peroxidation levels and the ratio of reduced GSH to GSSG...
January 12, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28087336/oleate-induces-katp-channel-dependent-hyperpolarization-in-mouse-hypothalamic-glucose-excited-neurons-without-altering-cellular-energy-charge
#7
Selma Dadak, Craig Beall, Julia M Vlachaki Walker, Marc P M Soutar, Rory J McCrimmon, Michael L J Ashford
The unsaturated fatty acid, oleate exhibits anorexigenic properties reducing food intake and hepatic glucose output. However, its mechanism of action in the hypothalamus has not been fully determined. This study investigated the effects of oleate and glucose on GT1-7 mouse hypothalamic cells (a model of glucose-excited (GE) neurons) and mouse arcuate nucleus (ARC) neurons. Whole-cell and perforated patch-clamp recordings, immunoblotting and cell energy status measures were used to investigate oleate- and glucose-sensing properties of mouse hypothalamic neurons...
January 9, 2017: Neuroscience
https://www.readbyqxmd.com/read/28042952/uncoupling-protein-2-downregulation-by-hypoxia-through-repression-of-peroxisome-proliferator-activated-receptor-%C3%AE-promotes-chemoresistance-of-non-small-cell-lung-cancer
#8
Mingxing Wang, Guoyin Li, Zhiwei Yang, Lei Wang, Lei Zhang, Ting Wang, Yimeng Zhang, Shengli Zhang, Yong Han, Lintao Jia
Hypoxic microenvironment is critically involved in the response of non-small cell lung cancer (NSCLC) to chemotherapy, the mechanisms of which remain largely unknown. Here, we found that NSCLC patients exhibited increased chemotherapeutic resistance when complicated by chronic obstructive pulmonary disease (COPD), a critical cause of chronic hypoxemia. The downregulation of uncoupling protein 2 (UCP2), which is attributed to hypoxia-inducible factor 1 (HIF-1)-mediated suppression of the transcriptional factor peroxisome proliferator-activated receptor γ (PPARγ), was involved in NSCLC chemoresistance, and predicted a poor survival rate of patients receiving routine chemotherapy...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27998096/small-molecule-uncoupling-protein-mimics-synthetic-anion-receptors-as-fatty-acid-activated-proton-transporters
#9
Xin Wu, Philip A Gale
Uncoupling proteins (UCPs) regulate energy expenditure in living cells by inducing proton leakage across the mitochondrial inner membrane, thereby uncoupling adenosine diphosphate phosphorylation from nutrient oxidation. The proton transport activity of UCP1 and UCP2 requires activation by fatty acids. We report here the first examples of synthetic neutral anion receptors performing this biologically important fatty acid-activated function in phospholipid bilayers. We have shown that a tripodal thiourea possesses poor H(+)/OH(-) transport activity without fatty acids, but in the presence of long-chain fatty acids is "switched on" as a proton transporter with an activity close to that of a commonly used protonophore...
December 21, 2016: Journal of the American Chemical Society
https://www.readbyqxmd.com/read/27994193/association-and-expression-analyses-of-the-ucp2-and-ucp3-gene-polymorphisms-with-body-measurement-and-meat-quality-traits-in-qinchuan-cattle
#10
Yaning Wang, Wucai Yang, Linsheng Gui, Hongbao Wang, Linsen Zan
The uncoupling proteins (UCPs) belong to the mitochondrial inner membrane anion carrier superfamily and play an important role in energy homeostasis. Genetic studies have demonstrated that Ucp2 and Ucp3 gene variants are involved in obesity and metabolic syndrome. The aim of this study was to identify associations between polymorphisms of Ucp2 and Ucp3 genes and economically-important traits in Qinchuan cattle. In the present study, one single-nucleotide polymorphism (SNP) in the 5'UTR region (SNP1:g.C-754G) of the Ucp2 gene was identified by direct sequencing of 441 Qinchuan cattle...
December 2016: Journal of Genetics
https://www.readbyqxmd.com/read/27989750/the-antioxidant-uncoupling-protein-2-stimulates-hnrnpa2-b1-glut1-and-pkm2-expression-and-sensitizes-pancreas-cancer-cells-to-glycolysis-inhibition
#11
Jessica Brandi, Daniela Cecconi, Marco Cordani, Margalida Torrens-Mas, Raffaella Pacchiana, Elisa Dalla Pozza, Giovanna Butera, Marcello Manfredi, Emilio Marengo, Jordi Oliver, Pilar Roca, Ilaria Dando, Massimo Donadelli
Several evidence indicate that metabolic alterations play a pivotal role in cancer development. Here, we report that the mitochondrial uncoupling protein 2 (UCP2) sustains the metabolic shift from mitochondrial oxidative phosphorylation (mtOXPHOS) to glycolysis in pancreas cancer cells. Indeed, we show that UCP2 sensitizes pancreas cancer cells to the treatment with the glycolytic inhibitor 2-deoxy-D-glucose. Through a bidimensional electrophoresis analysis, we identify 19 protein species differentially expressed after treatment with the UCP2 inhibitor genipin and, by bioinformatic analyses, we show that these proteins are mainly involved in metabolic processes...
October 27, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27980001/exogenous-thyroxine-improves-glucose-intolerance-in-insulin-resistant-rats
#12
Guillermo Vazquez-Anaya, Bridget Martinez, José G Soñanez-Organis, Daisuke Nakano, Akira Nishiyama, Rudy M Ortiz
Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T4) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T4 (8...
March 2017: Journal of Endocrinology
https://www.readbyqxmd.com/read/27967291/novel-hypoglycemia-phenotype-in-congenital-hyperinsulinism-due-to-dominant-mutations-of-uncoupling-protein-2-ucp2
#13
Christine T Ferrara, Kara E Boodhansingh, Elenora Paradies, Fiermonte Giuseppe, Linda J Steinkrauss, Lisa Swartz Topor, Jose Bernardo Quintos, Arupa Ganguly, Diva D De Leon, Ferdinando Palmieri, Charles A Stanley
CONTEXT: The rarest genetic form of congenital hyperinsulinism (HI) has been associated with dominant inactivating mutations in uncoupling protein 2 (UCP2), a mitochondrial inner membrane carrier that modulates the oxidation of glucose vs amino acids. OBJECTIVE: To evaluate the frequency of UCP2 mutations in children with HI and phenotypic features of this form of HI. DESIGN: We examined 211 children with diazoxide-responsive HI seen at The Children's Hospital of Philadelphia (CHOP) between 1997 and October 2016...
December 14, 2016: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/27966452/toxicity-assessment-of-hydrogen-peroxide-on-toll-like-receptor-system-apoptosis-and-mitochondrial-respiration-in-piglets-and-ipec-j2-cells
#14
Jie Yin, Miaomiao Wu, Yuying Li, Wenkai Ren, Hao Xiao, Shuai Chen, Chunyong Li, Bie Tan, Hengjia Ni, Xia Xiong, Yuzhe Zhang, Xingguo Huang, Rejun Fang, Tiejun Li, Yulong Yin
In this study, expressions of toll-like receptors (TLRs) and apoptosis-related genes in piglets and mitochondrial respiration in intestinal porcine epithelial cells were investigated after hydrogen peroxide (H2O2) exposure. The in vivo results showed that H2O2 influenced intestinal expressions of TLRs and apoptosis related genes. H2O2 treatment (5% and 10%) downregulated uncoupling protein 2 (UCP2) expression in the duodenum (P < 0.05), while low dosage of H2O2 significantly increased UCP2 expression in the jejunum (P < 0...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27919855/uncoupling-protein-2-deficiency-reduces-proliferative-capacity-of-murine-pancreatic-stellate-cells
#15
Sarah Muller, Sandra Maria Klingbeil, Andreea Sandica, Robert Jaster
BACKGROUND: Uncoupling protein 2 (UCP2) has been suggested to inhibit mitochondrial production of reactive oxygen species (ROS) by decreasing the mitochondrial membrane potential. Experimental acute pancreatitis is associated with increased UCP2 expression, whereas UCP2 deficiency retards regeneration of aged mice from acute pancreatitis. Here, we have addressed biological and molecular functions of UCP2 in pancreatic stellate cells (PSCs), which are involved in pancreatic wound repair and fibrogenesis...
December 2016: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/27919820/tnf-%C3%AE-and-cancer-cachexia-molecular-insights-and-clinical-implications
#16
REVIEW
Hetal J Patel, Bhoomika M Patel
Cancer cachexia characterized by a chronic wasting syndrome, involves skeletal muscle loss and adipose tissue loss and resistance to conventional nutritional support. Cachexia is responsible for the reduction in quality and length of life of cancer patients. It also decreases the muscle strength of the patients. The pro-inflammatory and pro-cachectic factors produced by the tumor cells have important role in genesis of cachexia. A number of pro-inflammatory cytokines, like interleukin-1 (IL-1), IL-6, tumor necrosis factor- alpha (TNF-α) may have important role in the pathological mechanisms of cachexia in cancer...
February 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/27916641/ucp1-the-mitochondrial-uncoupling-protein-of-brown-adipocyte-a%C3%A2-personal-contribution-and-a-historical-perspective
#17
REVIEW
Daniel Ricquier
The present text summarizes what was my contribution, starting in 1975, to the research on the uncoupling protein 1 (UCP1), the mitochondrial uncoupler of brown adipocytes. The research on UCP1 aimed at identifying the mechanisms of heat production by brown adipocytes that occurs in mammals either at birth or during cold exposure and arousal in hibernators. With others and in particular Dr. David Nicholls, I participated in the first experiments that contributed to the identification of UCP1. Important steps were the obtention of UCP1 antibodies followed with my main collaborator and friend Frédéric Bouillaud with the initial cloning of the UCP1 cDNA and gene from rats and humans...
March 2017: Biochimie
https://www.readbyqxmd.com/read/27903512/thyroid-hormone-stimulated-increases-in-pgc-1%C3%AE-and-ucp2-promote-life-history-specific-endocrine-changes-and-maintain-a-lipid-based-metabolism
#18
Bridget Martinez, José G Soñanez-Organis, Jose A Godoy-Lugo, Lillian Horin, Daniel E Crocker, Rudy M Ortiz
Thyroid hormones (TH) regulate metabolism, but are typically suppressed during times of stressful physiological conditions, including fasting. Interestingly, prolonged fasting in northern elephant seal pups is associated with reliance on a lipid-based metabolism and increased levels of circulating thyroid hormones that are partially attributed to active secretion as opposed to reduced clearance. This apparent paradox is coupled with complementary increases in cellular TH-mediated activity suggesting that in mammals naturally adapted to prolonged fasting TH are necessary to support metabolism...
November 30, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
https://www.readbyqxmd.com/read/27899181/corrigendum-to-short-chain-fatty-acids-induce-ucp2-mediated-autophagy-in-hepatic-cells-biochem-biophys-res-commun-480-2016-461-467
#19
Liliana F Iannucci, Jingfeng Sun, Brijesh K Singh, Jin Zhou, Vincent A Kaddai, Antonia Lanni, Paul M Yen, Rohit A Sinha
No abstract text is available yet for this article.
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27875726/the-association-of-uncoupling-protein-2-ucp2-exon-8-insertion-deletion-polymorphism-and-ecg-derived-qrs-duration-a-cross-sectional-study-in-an-australian-rural-population
#20
Yvonne Yin Leng Lee, Yuling Zhou, Herbert F Jelinek, Brett D Hambly, Craig S McLachlan
BACKGROUND: Associations between inherited mitochondrial disease and cardiac conduction have been previously described. However, there are no available studies exploring the mitochondrial uncoupling protein 2 gene (UCP2) insertion/deletion (I/D) polymorphisms interaction on cardiac electrical conduction. Our aim was to determine if ECG-derived QRS duration is associated with UCP2 DD genotype in a cross-sectional Australian aging rural population. METHODS: A retrospective study design utilizing a rural health diabetic screening clinic data-base containing observational data from September 2011 to September 2014...
February 1, 2017: International Journal of Cardiology
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