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Succinate dehydrogenase

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https://www.readbyqxmd.com/read/28099933/loss-of-maternal-chromosome-11-is-a-signature-event-in-sdhaf2-sdhd-and-vhl-related-paragangliomas-but-less-significant-in-sdhb-related-paragangliomas
#1
Attje S Hoekstra, Erik F Hensen, Ekaterina S Jordanova, Esther Korpershoek, Anouk Na van der Horst-Schrivers, Cees Cornelisse, Eleonora Pm Corssmit, Frederik J Hes, Jeroen C Jansen, Henricus Pm Kunst, Henri Jlm Timmers, Adrian Bateman, Diana Eccles, Judith Vmg Bovée, Peter Devilee, Jean-Pierre Bayley
Germline mutations in the succinate dehydrogenase (SDHA, SDHB, SDHC, SDHD, SDHAF2) or Von Hippel-Lindau (VHL) genes cause hereditary paraganglioma/pheochromocytoma. While SDHB (1p36) and VHL (3p25) are associated with autosomal dominant disease, SDHD (11q23) and SDHAF2 (11q13) show a remarkable parent-of-origin effect whereby tumor formation is almost completely dependent on paternal transmission of the mutant allele. Loss of the entire maternal copy of chromosome 11 occurs frequently in SDHD-linked tumors, and has been suggested to be the basis for this typical inheritance pattern...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28099845/absence-of-neurofibromin-induces-an-oncogenic-metabolic-switch-via-mitochondrial-erk-mediated-phosphorylation-of-the-chaperone-trap1
#2
Ionica Masgras, Francesco Ciscato, Anna Maria Brunati, Elena Tibaldi, Stefano Indraccolo, Matteo Curtarello, Federica Chiara, Giuseppe Cannino, Elena Papaleo, Matteo Lambrughi, Giulia Guzzo, Alberto Gambalunga, Marco Pizzi, Vincenza Guzzardo, Massimo Rugge, Stefania Edith Vuljan, Fiorella Calabrese, Paolo Bernardi, Andrea Rasola
Mutations in neurofibromin, a Ras GTPase-activating protein, lead to the tumor predisposition syndrome neurofibromatosis type 1. Here, we report that cells lacking neurofibromin exhibit enhanced glycolysis and decreased respiration in a Ras/ERK-dependent way. In the mitochondrial matrix of neurofibromin-deficient cells, a fraction of active ERK1/2 associates with succinate dehydrogenase (SDH) and TRAP1, a chaperone that promotes the accumulation of the oncometabolite succinate by inhibiting SDH. ERK1/2 enhances both formation of this multimeric complex and SDH inhibition...
January 17, 2017: Cell Reports
https://www.readbyqxmd.com/read/28096720/update-on-gastrointestinal-stromal-tumors-for-radiologists
#3
REVIEW
Sree Harsha Tirumani, Akshay D Baheti, Harika Tirumani, Ailbhe O'Neill, Jyothi P Jagannathan
The management of gastrointestinal stromal tumors (GISTs) has evolved significantly in the last two decades due to better understanding of their biologic behavior as well as development of molecular targeted therapies. GISTs with exon 11 mutation respond to imatinib whereas GISTs with exon 9 or succinate dehydrogenase subunit mutations do not. Risk stratification models have enabled stratifying GISTs according to risk of recurrence and choosing patients who may benefit from adjuvant therapy. Assessing response to targeted therapies in GIST using conventional response criteria has several potential pitfalls leading to search for alternate response criteria based on changes in tumor attenuation, volume, metabolic and functional parameters...
January 2017: Korean Journal of Radiology: Official Journal of the Korean Radiological Society
https://www.readbyqxmd.com/read/28088649/fumarate-reductase-superfamily-a-diverse-group-of-enzymes-whose-evolution-is-correlated-to-the-establishment-of-different-metabolic-pathways
#4
Douglas Jardim-Messeder, Caroline Cabreira-Cagliari, Rafael Rauber, Andreia Carina Turchetto-Zolet, Rogério Margis, Márcia Margis-Pinheiro
Fumarate and succinate are known to be present in prebiotic systems essential for the origin of life. The fumarate and succinate interconversion reactions have been conserved throughout evolution and are found in all living organisms. The fumarate and succinate interconversion is catalyzed by the enzymes succinate dehydrogenase (SDH) and fumarate reductase (FRD). In this work we show that SDH and FRD are part of a group of enzymes that we propose to designate "fumarate reductase superfamily". Our results demonstrate that these enzymes emerged from a common ancestor and were essential in the development of metabolic pathways involved in energy transduction...
January 11, 2017: Mitochondrion
https://www.readbyqxmd.com/read/28087904/-protective-effect-of-diosgenin-on-chondrocytes-mediated-by-jak2-stat3-signaling-pathway-in-mice-with-osteoarthritis
#5
Jun Liu, Xiaole He, Ping Zhen, Shenghu Zhou, Xusheng Li
Objective: To investigate the effect of diosgenin (Dgn) on chondrocytes and its relation to JAK2/STAT3 signaling pathway in mice with osteoarthritis (OA).Methods: Fifteen male C57BL/6 mice were randomly divided into three groups:control group, OA group and OA+Dgn group. After 4 weeks of treatment, the histopathological changes of cartilage tissue were observed by toluidine blue staining under light microscopy and the ultrastructure of chondrocytes was observed under electron microscopy. The primarily cultured chondrocytes of OA mice were randomly divided into 4 groups:(1) OA group, (2) Dgn group, (3) Dgn+AG490 group, (4) AG490 group...
May 25, 2016: Zhejiang da Xue Xue Bao. Yi Xue Ban, Journal of Zhejiang University. Medical Sciences
https://www.readbyqxmd.com/read/28087461/low-glucose-stress-decreases-cellular-nadh-and-mitochondrial-atp-in-colonic-epithelial-cancer-cells-influence-of-mitochondrial-substrates
#6
Magdalena L Circu, Ronald E Maloney, Tak Yee Aw
In this study, we investigated how colonic epithelial cells maintained pyridine nucleotide (NADH/NAD(+)) redox homeostasis upon acute metabolic variation imposed by glucose deprivation or supplementation with mitochondrial substrates, succinate and malate/glutamate (M/G). Our results showed that low glucose caused cellular NADH/NAD(+) redox imbalance that diminished lactate dehydrogenase (LDH) activity and resulted in lower lactate contents. The concurrent activation of malic enzyme (ME) suggested a role for malate in preserving cellular pyruvate that remained unchanged at low glucose...
January 10, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28080216/occurrence-of-mycotoxins-in-wheat-grains-exposed-to-fungicides-on-fusarium-head-blight-control-in-southern-brazil
#7
Leandro N Marques, Ionara R Pizzutti, Ricardo S Balardin, Ingrid D Dos Santos, Jonatan V Dias, Marlon T Stefanello, Pablo T Serafini
Mycotoxins occurrence in wheat grains impose risks to human and animal health. The southern Brazil has favorable weather conditions for Fusarium graminearum infections and consequently for mycotoxins accumulation on grains. The goal of this study was to evaluate the behavior of new wheat commercial genotypes to Fusarium Head Blight (FHB), to control performance of new fungicide formulations and their relationship with mycotoxins concentration in grains. The manly mycotoxin occurrence on wheat grains in southern Brazil was deoxynivalenol (DON)...
January 12, 2017: Journal of Environmental Science and Health. Part. B, Pesticides, Food Contaminants, and Agricultural Wastes
https://www.readbyqxmd.com/read/28074523/familial-gastrointestinal-stromal-tumors-lentigines-and-caf%C3%A3-au-lait-macules-associated-with-germline-c-kit-mutation-treated-with-imatinib
#8
Divya Gupta, Laxmisha Chandrashekar, Lidia Larizza, Elisa A Colombo, Laura Fontana, Cristina Gervasini, Devinder M Thappa, Medha Rajappa, Kalai Selvi Rajendiran, Gubbi Shamanna Sreenath, Vikram Kate
BACKGROUND: Familial lentiginosis syndromes are characterized by a wide array of manifestations resulting from activation of molecular pathways which control growth, proliferation, and differentiation of a broad range of tissues. Familial gastrointestinal stromal tumors (GISTs) are often accompanied by additional features like hyperpigmentation, mastocytosis, and dysphagia. They have been described with mutations in c-kit (most commonly), platelet-derived growth factor receptor A, neurofibromatosis-1, and succinate dehydrogenase genes...
February 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28070496/utility-of-the-succinate-fumarate-ratio-for-assessing-sdh-dysfunction-in-different-tumor-types
#9
Edward Kim, Michael Jp Wright, Loretta Sioson, Talia Novos, Anthony J Gill, Diana E Benn, Christopher White, Trisha Dwight, Roderick J Clifton-Bligh
OBJECTIVE: Mutations of genes encoding the four subunits of succinate dehydrogenase (SDH) have been associated with pheochromocytoma and paraganglioma (PPGLs), gastrointestinal stromal tumors (GISTs) and renal cell carcinomas (RCCs). These tumors have not been characterized in a way that reflects severity of SDH dysfunction. Mass spectrometric analysis now allows measurement of metabolites extracted from formalin fixed paraffin embedded (FFPE) specimens. We assess whether SDH deficiency in various tumor types characterized by loss of SDHB protein expression correlates with SDH dysfunction as assessed by the ratio of succinate:fumarate in FFPE specimens...
March 2017: Molecular Genetics and Metabolism Reports
https://www.readbyqxmd.com/read/28061458/oncometabolite-succinate-promotes-angiogenesis-by-upregulating-vegf-expression-through-gpr91-mediated-stat3-and-erk-activation
#10
Xianmin Mu, Ting Zhao, Che Xu, Wei Shi, Biao Geng, Jiajia Shen, Chen Zhang, Jinshun Pan, Jing Yang, Shi Hu, Yuanfang Lv, Hao Wen, Qiang You
Altered cellular metabolism is now generally acknowledged as a hallmark of cancer cells, the resultant abnormal oncometabolites cause both metabolic and nonmetabolic dysregulation and potential transformation to malignancy. A subset of cancers have been found to be associated with mutations in succinate dehydrogenase genes which result in the accumulation of succinate. However, the function of succinate in tumorigenesis remains unclear. In the present study, we aim to investigate the role of oncometabolite succinate in tumor angiogenesis...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28058510/homozygous-mutation-p-pro304his-in-idh3a-encoding-isocitrate-dehydrogenase-subunit-is-associated-with-severe-encephalopathy-in-infancy
#11
Aviva Fattal-Valevski, Hila Eliyahu, NItai D Fraenkel, Ganit Elmaliach, Moran Hausman-Kedem, Avraham Shaag, Dror Mandel, Ophry Pines, Orly Elpeleg
Mitochondrial encephalopathies are a heterogeneous group of disorders which generally carries a grave prognosis. Using exome sequencing, we identified a homozygous mutation, Pro-304-His in the IDH3A gene, in a patient suffering from infantile encephalopathy with peripheral and autonomic nervous system involvement. Mammalian isocitrate dehydrogenase (IDH) 3 is a heterotetramer of 2alfa, 1beta, and 1gamma subunits, and IDH3A encodes the alfa subunit of the mitochondrial NAD(+)-dependent IDH. Here we show that in contrast to wild-type human IDH3A, the human IDH3A which harbor the p...
January 2017: Neurogenetics
https://www.readbyqxmd.com/read/28057548/the-protection-effects-of-1e-6e-1-7-diphenylhepta-1-6-diene-3-5-dione-a-curcumin-analogue-against-operative-liver-injury-in-rats
#12
Xiaowei Chi, Dan Yu, Peijing Li, Qianfeng Lu, Wenjiao Jiang, Kun Hao
The relationship between the chemistry characteristic and the hepatoprotective effects of (1E,6E)-1,7-diphenylhepta-1,6-diene-3,5-dione (DDD), a curcumin analogue, in operative liver injury rats was investigated to reveal the mechanism of hepatic protection effects of DDD. DDD (1.2-4.8mmol/kg) was administrated 10min before reperfusion phase in hepatic ischemia-reperfusion injury (IRI) rats. DDD (4.8mmol/kg) administrated 10min before ischemia and N-acetylcysteine (NAC) (4.8mmol/kg) administrated 10min before reperfusion were included for comparative studies...
January 2, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28049145/the-fumarate-reductase-of-bacteroides-thetaiotaomicron-unlike-that-of-escherichia-coli-is-configured-so-that-it-does-not-generate-reactive-oxygen-species
#13
Zheng Lu, James A Imlay
: The impact of oxidative stress upon organismal fitness is most apparent in the phenomenon of obligate anaerobiosis. The root cause may be multifaceted, but the intracellular generation of reactive oxygen species (ROS) likely plays a key role. ROS are formed when redox enzymes accidentally transfer electrons to oxygen rather than to their physiological substrates. In this study, we confirm that the predominant intestinal anaerobe Bacteroides thetaiotaomicron generates intracellular ROS at a very high rate when it is aerated...
January 3, 2017: MBio
https://www.readbyqxmd.com/read/28044282/are-prepubertal-children-metabolically-comparable-to-well-trained-adult-endurance-athletes
#14
REVIEW
Sébastien Ratel, Anthony J Blazevich
It is well acknowledged that prepubertal children have smaller body dimensions and a poorer mechanical (movement) efficiency, and thus a lower work capacity than adults. However, the scientific evidence indicates that prepubertal children have a greater net contribution of energy derived from aerobic metabolism in exercising muscle and reduced susceptibility to muscular fatigue, which makes them metabolically comparable to well-trained adult endurance athletes. For example, the relative energy contribution from oxidative and non-oxidative (i...
January 2, 2017: Sports Medicine
https://www.readbyqxmd.com/read/28043329/evaluation-of-the-toxicity-of-fungicides-to-flight-muscle-mitochondria-of-bumblebee-bombus-terrestris-l
#15
Mikhail Y Syromyatnikov, Anastasia V Kokina, Alexey V Lopatin, Anatoly A Starkov, Vasily N Popov
Insects pollinate 75% of crops used for human consumption. Over the last decade, a substantial reduction in the abundance of pollinating insects has been recorded and recognized as a severe matter for food supply security. Many of the important food crops destined for human consumption are grown in greenhouses. A unique feature of greenhouse agriculture is the extensive use of fungicides to curb multiple fungal infections. The most widely used pollinating insects in greenhouses are commercially reared bumblebees...
January 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28039307/sdh6-and-sdh7-contribute-to-anchoring-succinate-dehydrogenase-to-the-inner-mitochondrial-membrane-in-arabidopsis-thaliana
#16
Christine Schikowsky, Jennifer Senkler, Hans-Peter Braun
The succinate dehydrogenase complex (complex II) is a highly conserved protein com-plex composed of the SDH1-SDH4 subunits in bacteria and in the mitochondria of ani-mals and fungi. The reason for the occurrence of up to four additional subunits in com-plex II of plants, termed SDH5-SDH8, so far is a mystery. We here present a biochemi-cal approach to investigate the internal subunit arrangement of Arabidopsis complex II. Using low-concentration detergent treatments the holo complex is dissected into sub-complexes which are analyzed by a three-dimensional gel electrophoresis system...
December 30, 2016: Plant Physiology
https://www.readbyqxmd.com/read/28036268/role-of-vhl-hif1a-and-sdh-on-the-expression-of-mir-210-implications-for-tumoral-pseudo-hypoxic-fate
#17
Anna Merlo, Cristóbal Bernardo-Castiñeira, Inés Sáenz-de-Santa-María, Ana S Pitiot, Milagros Balbín, Aurora Astudillo, Nuria Valdés, Bartolomé Scola, Raquel Del Toro, Simón Méndez-Ferrer, José I Piruat, Carlos Suarez, María-Dolores Chiara
The hypoxia-inducible factor 1α (HIF-1α) and its microRNA target, miR-210, are candidate tumor-drivers of metabolic reprogramming in cancer. Neuroendocrine neoplasms such as paragangliomas (PGLs) are particularly appealing for understanding the cancer metabolic adjustments because of their associations with deregulations of metabolic enzymes, such as succinate dehydrogenase (SDH), and the von Hippel Lindau (VHL) gene involved in HIF-1α stabilization. However, the role of miR-210 in the pathogenesis of SDH-related tumors remains an unmet challenge...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28032215/a-driver-role-for-gaba-metabolism-in-controlling-stem-and-proliferative-cell-state-through-ghb-production-in-glioma
#18
Elias A El-Habr, Luiz G Dubois, Fanny Burel-Vandenbos, Alexandra Bogeas, Joanna Lipecka, Laurent Turchi, François-Xavier Lejeune, Paulo Lucas Cerqueira Coehlo, Tomohiro Yamaki, Bryan M Wittmann, Mohamed Fareh, Emna Mahfoudhi, Maxime Janin, Ashwin Narayanan, Ghislaine Morvan-Dubois, Charlotte Schmitt, Maité Verreault, Lisa Oliver, Ariane Sharif, Johan Pallud, Bertrand Devaux, Stéphanie Puget, Penelope Korkolopoulou, Pascale Varlet, Chris Ottolenghi, Isabelle Plo, Vivaldo Moura-Neto, Thierry Virolle, Hervé Chneiweiss, Marie-Pierre Junier
Cell populations with differing proliferative, stem-like and tumorigenic states co-exist in most tumors and especially malignant gliomas. Whether metabolic variations can drive this heterogeneity by controlling dynamic changes in cell states is unknown. Metabolite profiling of human adult glioblastoma stem-like cells upon loss of their tumorigenicity revealed a switch in the catabolism of the GABA neurotransmitter toward enhanced production and secretion of its by-product GHB (4-hydroxybutyrate). This switch was driven by succinic semialdehyde dehydrogenase (SSADH) downregulation...
December 28, 2016: Acta Neuropathologica
https://www.readbyqxmd.com/read/28027118/gain-of-tp53-mutation-in-imatinib-treated-sdh-deficient-gastrointestinal-stromal-tumor-and-clinical-utilization-of-targeted-next-generation-sequencing-panel-for-therapeutic-decision-support
#19
Christina H Wei, Jonas Pettersson, Mihaela Campan, Shefali Chopra, Wesley Naritoku, Sue E Martin, Pamela M Ward
Patients with succinate dehydrogenase (SDH)-deficient gastrointestinal stromal tumor (GIST) have few therapeutic options. Despite lack of KIT or platelet-derived growth factor receptor A (PDGFRA) driver mutations, SDH-deficient GISTs display strong expression of KIT by immunohistochemistry and these patients are often treated with tyrosine kinase inhibitors, including imatinib as a first-line therapy. Using a targeted next-generation sequencing panel of mutation hotspots of 50-clinically relevant genes, we investigated (1) concurrence of somatic/actionable mutations and (2) tumor molecular evolution by comparing 2 resection specimens 1...
December 23, 2016: Applied Immunohistochemistry & Molecular Morphology: AIMM
https://www.readbyqxmd.com/read/28024286/taurine-treatment-preserves-brain-and-liver-mitochondrial-function-in-a-rat-model-of-fulminant-hepatic-failure-and-hyperammonemia
#20
Akram Jamshidzadeh, Reza Heidari, Mozhgan Abasvali, Mehdi Zarei, Mohammad Mehdi Ommati, Narges Abdoli, Forouzan Khodaei, Yasaman Yeganeh, Faezeh Jafari, Azita Zarei, Zahra Latifpour, Elnaz Mardani, Negar Azarpira, Behnam Asadi, Asma Najibi
Ammonia-induced mitochondrial dysfunction and energy crisis is known as a critical consequence of hepatic encephalopathy (HE). Hence, mitochondria are potential targets of therapy in HE. The current investigation was designed to evaluate the role of taurine treatment on the brain and liver mitochondrial function in a rat model of hepatic encephalopathy and hyperammonemia. The animals received thioacetamide (400mg/kg, i.p, for three consecutive days at 24-h intervals) as a model of acute liver failure and hyperammonemia...
December 23, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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