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https://www.readbyqxmd.com/read/29351723/mitochondrial-uncoupling-proteins-subtle-regulators-of-cellular-redox-signaling
#1
Petr Jezek, Blanka Holendová, Keith D Garlid, Martin Jaburek
SIGNIFICANCE: Mitochondria are the energetic, metabolic, redox and information signaling centers of the cell. Substrate pressure, mitochondrial network dynamics and cristae morphology state are integrated by the protonmotive force Δp or its potential component, ΔΨ, which are attenuated by proton backflux into the matrix, termed uncoupling. The mitochondrial uncoupling proteins (UCP1-5) play an eminent role in the regulation of each of the above aspects, being involved in numerous physiological events including redox signaling...
January 19, 2018: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/29348686/defects-in-the-mitochondrial-trna-modification-enzymes-mto1-and-gtpbp3-promote-different-metabolic-reprogramming-through-a-hif-ppar%C3%AE-ucp2-ampk-axis
#2
Rachid Boutoual, Salvador Meseguer, Magda Villarroya, Elena Martín-Hernández, Mohammed Errami, Miguel A Martín, Marta Casado, M-Eugenia Armengod
Human proteins MTO1 and GTPBP3 are thought to jointly catalyze the modification of the wobble uridine in mitochondrial tRNAs. Defects in each protein cause infantile hypertrophic cardiomyopathy with lactic acidosis. However, the underlying mechanisms are mostly unknown. Using fibroblasts from an MTO1 patient and MTO1 silenced cells, we found that the MTO1 deficiency is associated with a metabolic reprogramming mediated by inactivation of AMPK, down regulation of the uncoupling protein 2 (UCP2) and transcription factor PPARγ, and activation of the hypoxia inducible factor 1 (HIF-1)...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29325933/sestrin2-prevents-age-related-intolerance-to-post-myocardial-infarction-via-ampk-pgc-1%C3%AE-pathway
#3
Nanhu Quan, Lin Wang, Xu Chen, Chelsea Luckett, Courtney Cates, Thomas Rousselle, Yang Zheng, Ji Li
We have revealed that a novel stress-inducible protein, Sestrin2, declines in the heart with aging. Moreover, there is an interaction between Sestrin2 and energy sensor AMPK in the heart in response to ischemic stress. The objective of this study is to determine whether Sestrin2-AMPK complex modulates PGC-1α in the heart and protects the heart from ischemic insults. In order to characterize the role of cardiac Sestrin2-AMPK signaling cascade in aging, C57BL/6 wild type young mice (3-4months), aged mice (24-26months) and young Sestrin2 KO mice were subjected to left anterior descending coronary artery occlusion for in vivo regional ischemia...
January 8, 2018: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/29280746/congenital-hyperinsulinism-diagnosis-and-treatment-update
#4
Hüseyin Demirbilek, Khalid Hussain
Pancreatic β-cells are finely tuned to secrete insulin so that plasma glucose levels are maintained within a narrow physiological range (3.5-5.5 mmol/L). Hyperinsulinaemic hypoglycaemia (HH) is the inappropriate seretion of insulin in the presence of low plasma glucose levels and leads to severe and persistent hypoglycaemia in neonates and children. Mutations in 12 different key genes (ABCC8, KCNJ11, GLUD1, GCK, HADH, SLC16A1, UCP2, HNF4A, HNF1A, HK1, PGM1 and PMM2) that are involved in the regulation of insulin secretion from pancreatic β-cells have been described to be responsible for the underlying molecular mechanisms leading to congenital HH...
December 27, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29273197/relationship-between-estrogen-and-body-composition-energy-and-endocrine-factors-in-obese-women-with-normal-and-low-ree
#5
Somaye Ahmadi, Mohammad Reza Eshraghian, Mehdi Hedayati, Hamideh Pishva
OBJECTIVE: The aim of this study was to investigate the relationship between estrogen and leptin, thyroid(T3), Uncoupling Protein2(UCP2), sex hormone binding globulin(SHBG), and resting energy expenditure(REE) in obese subjects with normal and low REE, and to investigate the relationship of estrogen with body composition and energy intake. METHOD: A total 49 subjects (25-50 years old) were selected. Anthropometric measurements, body composition, and resting energy expenditure were measured...
December 19, 2017: Steroids
https://www.readbyqxmd.com/read/29221144/ucp2-overexpression-enhanced-glycolysis-via-activation-of-pfkfb2-during-skin-cell-transformation
#6
Annapoorna Sreedhar, Petra Petruska, Sumitra Miriyala, Manikandan Panchatcharam, Yunfeng Zhao
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane transporter which is often upregulated in human cancers. However, how this anion transporter affects tumorigenesis is not well understood. Using the skin cell transformation JB6 model, we demonstrated that UCP2 overexpression activated phosphofructokinase 2/fructose-2,6-bisphosphatase 2 (PFKFB2), a key regulator of glycolysis. In conjunction, upregulation of PFKFB2 expression correlated with elevated fructose 2,6-bisphosphate (Fru-2,6-P2) levels, 6-phosphofructo-1-kinase (PFK-1) activity, glucose uptake, and lactate production...
November 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29193738/cooperative-role-of-the-glp-1-receptor-and-%C3%AE-3-adrenergic-mediated-signaling-on-fat-mass-reduction-through-the-down-regulation-of-pka-akt-ampk-signaling-in-the-adipose-tissue-and-muscle-of-rats
#7
Juan Decara, Patricia Rivera, Sergio Arrabal, Antonio Vargas, Antonia Serrano, Francisco Javier Pavón, Carlos Dieguez, Rubén Nogueiras, Fernando Rodríguez de Fonseca, Juan Suárez
AIM: To explore the cooperation of GLP-1 receptor and β3-adrenergic receptor-mediated signaling in the control of fat mass/feeding behavior by studying the effects of a combined therapy composed of the GLP-1R agonist liraglutide and the β3-AR agonist CL316243. METHODS: The study included the analysis of key mechanisms regulating lipid/cholesterol metabolism, and thermogenesis in brown (BAT) and epididymal white (eWAT) adipose tissues, abdominal muscle and liver of male rats...
November 28, 2017: Acta Physiologica
https://www.readbyqxmd.com/read/29187642/irisin-protects-mitochondria-function-during-pulmonary-ischemia-reperfusion-injury
#8
Ken Chen, Zaicheng Xu, Yukai Liu, Zhen Wang, Yu Li, Xuefei Xu, Caiyu Chen, Tianyang Xia, Qiao Liao, Yonggang Yao, Cindy Zeng, Duofen He, Yongjian Yang, Tao Tan, Jianxun Yi, Jingsong Zhou, Hua Zhu, Jianjie Ma, Chunyu Zeng
Limb remote ischemic preconditioning (RIPC) is an effective means of protection against ischemia/reperfusion (IR)-induced injury to multiple organs. Many studies are focused on identifying endocrine mechanisms that underlie the cross-talk between muscle and RIPC-mediated organ protection. We report that RIPC releases irisin, a myokine derived from the extracellular portion of fibronectin domain-containing 5 protein (FNDC5) in skeletal muscle, to protect against injury to the lung. Human patients with neonatal respiratory distress syndrome show reduced concentrations of irisin in the serum and increased irisin concentrations in the bronchoalveolar lavage fluid, suggesting transfer of irisin from circulation to the lung under physiologic stress...
November 29, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29163755/uncoupling-protein-2-a-key-player-and-a-potential-therapeutic-target-in-vascular-diseases
#9
REVIEW
Giorgia Pierelli, Rosita Stanzione, Maurizio Forte, Serena Migliarino, Marika Perelli, Massimo Volpe, Speranza Rubattu
Uncoupling protein 2 (UCP2) is an inner mitochondrial membrane protein that belongs to the uncoupling protein family and plays an important role in lowering mitochondrial membrane potential and dissipating metabolic energy with prevention of oxidative stress accumulation. In the present article, we will review the evidence that UCP2, as a consequence of its roles within the mitochondria, represents a critical player in the predisposition to vascular disease development in both animal models and in humans, particularly in relation to obesity, diabetes, and hypertension...
2017: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29158541/dysregulation-of-mitochondrial-function-and-biogenesis-modulators-in-adipose-tissue-of-obese-children
#10
R Zamora-Mendoza, H Rosas-Vargas, M T Ramos-Cervantes, P Garcia-Zuniga, H Perez-Lorenzana, P Mendoza-Lorenzo, A Perez-Ortiz, J Estrada, A Miliar-Garcia, E Lara-Padilla, G Ceballos, A Rodriguez, F Villarreal, I Ramirez-Sanchez
BACKGROUND/OBJECTIVES: We aimed to evaluate mitochondrial biogenesis (MB), structure, metabolism, and dysfunction in abdominal adipose tissue from male pediatric patients with obesity. SUBJECTS/METHODS: Samples were collected from five children with obesity (percentile ⩾95) and five eutrophic boys (percentile ⩾5/⩽85) (8-12 years old) following parental informed consent. We analyzed the expression of key genes involved in MB (SIRT1, PPARγ, PGC1α, NRF1, NRF2, and TFAM) and surrogates for mitochondrial function/structure/metabolism (porin, TOMM20, complex I and V, UCP1, UCP2, SIRT3, SOD2) by Western blot...
November 21, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29154935/ghrelin-alleviates-paclitaxel-induced-peripheral-neuropathy-by-reducing-oxidative-stress-and-enhancing-mitochondrial-anti-oxidant-functions-in-mice
#11
Nobuyuki Ishii, Hironobu Tsubouchi, Ayako Miura, Shigehisa Yanagi, Hiroaki Ueno, Kazutaka Shiomi, Masamitsu Nakazato
Paclitaxel is an effective chemotherapeutic agent, but has some treatment-limiting adverse effects that markedly decrease patients' quality of life. Peripheral neuropathy is one of these, and no treatment for it has been established yet. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor, is secreted from the stomach and has widespread effects on multiple systems. We investigated the pharmacological potential of ghrelin in preventing paclitaxel-induced peripheral neuropathy using wild-type mice, ghrelin-null mice, and growth hormone secretagogue receptor-null mice...
November 15, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29154852/the-mitochondrial-uncoupling-protein-2-gene-is-causal-for-the-spontaneous-polycystic-liver-diseases-in-mice
#12
Misa Hirose, Paul Schilf, Sarah Rohde, Yask Gupta, Tiphaine Sancerni, Marie-Clotilde Alves-Guerra, Christian Sina, Robert Jaster, Bruno Miroux, Saleh M Ibrahim
Polycystic liver diseases (PCLDs) are autosomal dominant disorders. To date, 3 genes are known to be associated with the disease, SEC63 and PRKCSH and LRP5. Here, we report that mice deficient in the mitochondrial uncoupling protein 2 gene (Ucp2(-/-)) spontaneously developed PCLDs when they were over 12months old. Macroscopical observation, blood chemistry as well as histopathological analysis demonstrated the PCLDs found in Ucp2(-/-) mice were very similar to the findings in human PCLDs. This is the first report describing the gene encoding mitochondrial protein is causative for PCLDs...
November 14, 2017: Mitochondrion
https://www.readbyqxmd.com/read/29151065/the-mrna-expression-levels-of-uncoupling-proteins-1-and-2-in-mononuclear-cells-from-patients-with-metabolic-disorders-obesity-and-type-2-diabetes-mellitus
#13
Sona Margaryan, Agata Witkowicz, Anna Partyka, Levon Yepiskoposyan, Gayane Manukyan, Lidia Karabon
INTRODUCTION: Type 2 diabetes mellitus (T2DM) and obesity are metabolic disorders whose major hallmark is insulin resistance. Impaired mitochondrial activity, such as reduced ratio of energy production to respiration, has been implicated in the development of insulin resistance. Uncoupling proteins (UCPs) are proton carriers, expressed in the mitochondrial inner membrane, that uncouple oxygen consumption by the respiratory chain from ATP synthesis. AIM: The aim of the study was to determine transcriptional levels of UCP1 and UCP2 in peripheral blood mononuclear cells (PBMCs) from patients with metabolic disorders: T2DM, obesity and from healthy individuals...
October 19, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/29121676/naringin-prevents-hiv-1-protease-inhibitors-induced-metabolic-complications-in-vivo
#14
Sanelisiwe Nzuza, Sindiswa Zondi, Peter M O Owira
BACKGROUND: Insulin resistance, glucose intolerance and overt diabetes are known metabolic complications associated with chronic use of HIV-Protease Inhibitors. Naringin is a grapefruit-derived flavonoid with anti-diabetic, anti-dyslipidemia, anti-inflammatory and anti-oxidant activities. OBJECTIVES: The study investigated the protective effects of naringin on glucose intolerance and impaired insulin secretion and signaling in vivo. METHODS: Male Wistar rats were divided into six groups (n = 6) and were daily orally treated with distilled water {3...
2017: PloS One
https://www.readbyqxmd.com/read/29113301/ucp2-and-prmt1-are-key-prognostic-markers-for-lung-carcinoma-patients
#15
Corina T Madreiter-Sokolowski, Balázs Győrffy, Christiane Klec, Armin A Sokolowski, Rene Rost, Markus Waldeck-Weiermair, Roland Malli, Wolfgang F Graier
Cancer cells have developed unique strategies to meet their high energy demand. Therefore, they have established a setting of Ca(2+)-triggered high mitochondrial activity. But mitochondrial Ca(2+) uptake has to be strictly controlled to avoid mitochondrial Ca(2+) overload that would cause apoptotic cell death. Methylation by protein arginine methyl transferase 1 (PRMT1) desensitizes the mitochondrial Ca(2+) uptake machinery and reduces mitochondrial Ca(2+) accumulation in cancer cells. In case of PRMT1-driven methylation, proper mitochondrial Ca(2+) uptake is reestablished by increased activity of uncoupling protein 2 (UCP2), pointing to an importance of these proteins for cancer cell survival and activity...
October 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081505/serotonin-prevents-differentiation-into-brown-adipocytes-and-induces-trans-differentiation-into-white-adipocytes
#16
S Rozenblit-Susan, N Chapnik, O Froy
BACKGROUND/OBJECTIVES: Serotonin is synthesized by many cells in the periphery to affect vasoconstriction, intestinal motility, and glucose and lipid metabolism. It has recently been shown that serotonin leads to fat accumulation in white adipose tissue (WAT). However, the direct effect of serotonin on adipose tissue (BAT) differentiation and metabolism is limited. Therefore, our aim was to investigate the effect of serotonin on brown adipocyte metabolism and differentiation. METHODS: Non-differentiated HIB1B cells and differentiated HIB1B brown adipocytes were treated with serotonin and their metabolism and differentiation examined...
October 30, 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/29079704/mitochondrial-protein-ucp2-controls-pancreas-development
#17
Benjamin Broche, Selma Ben Fradj, Esther Aguilar, Tiphaine Sancerni, Matthieu Bénard, Fatna Makaci, Claire Berthault, Raphaël Scharfmann, Marie-Clotilde Alves-Guerra, Bertrand Duvillié
The mitochondrial carrier uncoupling protein (UCP) 2 belongs to the family of the UCPs. Despite its name, it is now accepted that UCP2 is rather a metabolite transporter than a UCP. UCP2 can regulate oxidative stress and/or energetic metabolism. In rodents, UCP2 is involved in the control of α- and β-cell mass as well as insulin and glucagon secretion. Our aim was to determine whether the effects of UCP2 observed on β-cell mass have an embryonic origin. Thus, we used Ucp2 knockout mice. We found an increased size of the pancreas in Ucp2-/- fetuses at embryonic day 16...
January 2018: Diabetes
https://www.readbyqxmd.com/read/29070699/inhibition-of-pyruvate-dehydrogenase-kinase-improves-pulmonary-arterial-hypertension-in-genetically-susceptible-patients
#18
Evangelos D Michelakis, Vikram Gurtu, Linda Webster, Gareth Barnes, Geoffrey Watson, Luke Howard, John Cupitt, Ian Paterson, Richard B Thompson, Kelvin Chow, Declan P O'Regan, Lan Zhao, John Wharton, David G Kiely, Adam Kinnaird, Aristeidis E Boukouris, Chris White, Jayan Nagendran, Darren H Freed, Stephen J Wort, J Simon R Gibbs, Martin R Wilkins
Pulmonary arterial hypertension (PAH) is a progressive vascular disease with a high mortality rate. It is characterized by an occlusive vascular remodeling due to a pro-proliferative and antiapoptotic environment in the wall of resistance pulmonary arteries (PAs). Proliferating cells exhibit a cancer-like metabolic switch where mitochondrial glucose oxidation is suppressed, whereas glycolysis is up-regulated as the major source of adenosine triphosphate production. This multifactorial mitochondrial suppression leads to inhibition of apoptosis and downstream signaling promoting proliferation...
October 25, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/29061315/metallothionein-prevents-doxorubicin-cardiac-toxicity-by-indirectly-regulating-the-uncoupling-proteins-2
#19
Li Jing, Man Yang, Yang Li, Yang Yu, Baolu Liang, Lige Cao, Xianqing Zhou, Shuangqing Peng, Zhiwei Sun
Doxorubicin (Dox) is a broad-spectrum anticancer agent, but its clinical use is restricted due to irreversible cardiac toxicity. Metallothionein (MT) can inhibit Dox-induced cardiac toxicity. Applying a proteomics approach we determined that uncoupling proteins (UCPs) may be implicated in this process. This study was designed to examine the mechanisms of MT against Dox cardiac toxicity and the link between MT and UCP2. In vivo, wild-type (MT(+/+)) and MT-I/II null (MT(-/-)) mice were given a single dose of Dox (15 mg/kg, i...
October 20, 2017: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29043564/the-ucp2-866g-a-polymorphism-could-be-considered-as-a-genetic-marker-of-different-functional-prognosis-in-ischemic-stroke-after-recanalization
#20
I Díaz-Maroto Cicuéndez, E Fernández-Díaz, J García-García, J Jordán, I Fernández-Cadenas, J Montaner, G Serrano-Heras, T Segura
Recent studies based on experimental animal models of stroke have suggested that uncoupling protein 2 (UCP2), an inner mitochondrial membrane protein that is thought to regulate energy metabolism and reduce reactive oxygen species generation, provides protection against reperfusion damage. We aimed to investigate whether -866G/A polymorphism in the promoter of the UCP2 gene, which enhances its transcriptional activity, is associated with functional prognosis in patients with embolic ischemic stroke after early recanalization...
December 2017: Neuromolecular Medicine
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