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Succinate dehydrogenase

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https://www.readbyqxmd.com/read/28523727/synthesis-and-antineoplastic-evaluation-of-mitochondrial-complex-ii-succinate-dehydrogenase-inhibitors-derived-from-atpenin-a5
#1
Hezhen Wang, Bader Huwaimel, Kshitij Verma, James Miller, Todd Germain, Nihar Kinarivala, Dimitri Pappas, Paul Brookes, Paul Charles Trippier
Mitochondrial complex II (CII) is an emerging target for numerous human diseases. Sixteen analogues of the CII inhibitor natural product atpenin A5 were prepared to evaluate the structure-activity relationship of the C-5 pyridine side chain. The side chain ketone moiety was determined to be pharmacophoric, engendering a bioactive conformation. Analogue 16c displayed CII IC50 = 64 nM, retained selectivity for CII over mitochondrial complex I (>156-fold) and possessed a ligand-lipophilicity efficiency of 5...
May 18, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28522764/obesity-induced-discrepancy-between-contractile-and-metabolic-phenotypes-in-slow-and-fast-twitch-skeletal-muscles-of-female-obese-zucker-rats
#2
Luz M Acevedo, Ana I Raya, Rafael Ríos, Escolástico Aguilera-Tejero, Jose-Luis L Rivero
A clear picture of skeletal muscle adaptations to obesity and related comorbidities remains elusive. This study describes fiber-type characteristics (size, proportions, and oxidative enzyme activity) in two typical hind limb muscles with opposite structure and function in an animal model of genetic obesity. Lesser fiber diameter, fiber type composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of muscle fiber types were assessed in slow- (soleus) and fast-twitch (tibialis cranialis) muscles of obese Zucker rats, and compared with age- (16 weeks) and sex-matched (females) lean Zucker rats (N=16/group)...
May 18, 2017: Journal of Applied Physiology
https://www.readbyqxmd.com/read/28514731/antagonistic-effects-of-selenium-on-cadmium-induced-apoptosis-by-restoring-the-mitochondrial-dynamic-equilibrium-and-energy-metabolism-in-chicken-spleens
#3
Zhe Xu, Xi Jin, Tingru Pan, Tianqi Liu, Na Wan, Shu Li
The aim of this study was to investigate the mechanism of cadmium-induced apoptosis in chicken spleens and the antagonistic effects of selenium. We duplicated the selenium-cadmium interaction model and examined the expression of apoptosis-, immune-, mitochondrial dynamics- and energy metabolism-related genes. The results demonstrated that after treatment with cadmium, the frequency of apoptosis was significantly increased, and the morphological characteristics of apoptosis were observed. The expression of pro-apoptotic genes was increased, and that of anti-apoptotic genes was decreased...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512002/cell-surface-g-protein-coupled-receptors-for-tumor-associated-metabolites-a-direct-link-to-mitochondrial-dysfunction-in-cancer
#4
REVIEW
Bojana Ristic, Yangzom D Bhutia, Vadivel Ganapathy
Mitochondria are the sites of pyruvate oxidation, citric acid cycle, oxidative phosphorylation, ketogenesis, and fatty acid oxidation. Attenuation of mitochondrial function is one of the most significant changes that occurs in tumor cells, directly linked to oncogenesis, angiogenesis, Warburg effect, and epigenetics. In particular, three mitochondrial enzymes are inactivated in cancer: pyruvate dehydrogenase (PDH), succinate dehydrogenase (SDH), and 3-hydroxy-3-methylglutaryl CoA synthase-2 (HMGCS2). These enzymes are subject to regulation via acetylation/deacetylation...
May 13, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28508835/beneficial-influence-of-ellagic-acid-on-biochemical-indexes-associated-with-experimentally-induced-colon-carcinogenesis
#5
Umesalma Syed, Sudhandiran Ganapasam
OBJECTIVE: To elucidate the key biochemical indexes associated with 1, 2-dimethylhydrazine (DMH)-induced colon carcinogenesis and the modulatory efficacy of a dietary polyphenol, ellagic acid (EA). MATERIALS AND METHODS: Wistar rats were chosen to study objective, and were divided into 4 groups; Group 1-control rats; Group 2-rats received EA (60 mg/kg body weight/day, orally); rats in Group 3-induced with DMH (20 mg/kg body weight) subcutaneously for 15 weeks; DMH-induced Group 4 rats were initiated with EA treatment...
January 2017: Journal of Cancer Research and Therapeutics
https://www.readbyqxmd.com/read/28508602/succinate-dehydrogenase-deficient-paragangliomas-pheochromocytomas-genetics-clinical-aspects-and-mini-review
#6
Larisa Rusyn, Brenda Kohn
No abstract text is available yet for this article.
March 2017: Pediatric Endocrinology Reviews: PER
https://www.readbyqxmd.com/read/28500238/sdha-mutated-paragangliomas-may-be-at-high-risk-of-metastasis
#7
Nicola Tufton, Rahul Ghelani, Umasuthan Srirangalingam, V K Ajith Kumar, William Drake, Donato Iacovazzo, Kassiani Skordilis, Daniel M Berney, Ma'en Al-Mrayat, Bernard Khoo, Scott Akker
We report the clinical outcomes of eleven patients with succinate dehydrogenase subunit A (SDHA) germline mutations from three UK tertiary referral centres to highlight a more diverse and expanding clinical spectrum of associated phenotypes. We suggest that SDHA paraganglioma related disease is not a low risk condition as first described. Of our six index cases, two developed metastatic disease and a further one had local vascular invasion. One patient developed multiple metachronous disease. Therefore, we believe these patients, like those with SDHB & SDHD mutations, should be part of a surveillance programme...
May 12, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28490599/the-phenotype-of-sdhb-germline-mutation-carriers-a-nationwide-study
#8
Nicolasine D Niemeijer, Johannes A Rijken, Karin Eijkelenkamp, A N A van der Horst-Schrivers, Michiel N Kerstens, Carli M Tops, Anouk van Berkel, Henri J Timmers, Henricus P M Kunst, C Rene Leemans, Peter H Bisschop, Koen Ma Dreijerink, Marieke van Dooren, Jean-Pierre Bayley, Alberto M Pereira, Jeroen Jansen, Frederik J Hes, Erik Hensen, E P Corssmit
Objective Succinate dehydrogenase B subunit (SDHB) gene germline mutations predispose to pheochromocytomas, sympathetic paragangliomas, head and neck paragangliomas, and non-paraganglionic tumors (e.g. renal cell carcinoma, gastrointestinal stromal tumor and pituitary neoplasia). The aim of this study was to determine phenotypical characteristics of a large Dutch cohort of SDHB germline mutation carriers and assess differences in clinical phenotypes related to specific SDHB mutations. Design Retrospective descriptive study...
May 10, 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28484812/metabolic-engineering-of-gluconobacter-oxydans-621h-for-increased-biomass-yield
#9
Ines Kiefler, Stephanie Bringer, Michael Bott
The obligatory aerobic acetic acid bacterium Gluconobacter oxydans incompletely oxidizes carbon sources regio- and stereoselectively in the periplasm and therefore is used industrially for oxidative biotransformations, e. g., in vitamin C production. However, it has a very low biomass yield as the oxidized products largely remain in the medium and cannot be used for anabolism. Cytoplasmic carbon metabolism occurs via the pentose phosphate pathway and the Entner-Doudoroff pathway, whereas glycolysis and the tricarboxylic acid cycle are incomplete...
May 8, 2017: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/28484589/idh1-or-2-mutations-do-not-predict-outcome-and-do-not-cause-loss-of-5-hydroxymethylcytosine-or-altered-histone-modifications-in-central-chondrosarcomas
#10
Arjen H G Cleven, Johnny Suijker, Georgios Agrogiannis, Inge H Briaire-de Bruijn, Norma Frizzell, Attje S Hoekstra, Pauline M Wijers-Koster, Anne-Marie Cleton-Jansen, Judith V M G Bovée
BACKGROUND: Mutations in isocitrate dehydrogenase (IDH)1 or -2 are found in ~50% of conventional central chondrosarcomas and in up to 87% of their assumed benign precursors enchondromas. The mutant enzyme acquires the activity to convert α-ketoglutarate into the oncometabolite d-2-hydroxyglutarate (d-2-HG), which competitively inhibits α-ketoglutarate dependent enzymes such as histone- and DNA demethylases. METHODS: We therefore evaluated the effect of IDH1 or -2 mutations on histone modifications (H3K4me3, H3K9me3 and H3K27me3), chromatin remodeler ATRX expression, DNA modifications (5-hmC and 5-mC), and TET1 subcellular localization in a genotyped cohort (IDH, succinate dehydrogenase (SDH) and fumarate hydratase (FH)) of enchondromas and central chondrosarcomas (n = 101) using immunohistochemistry...
2017: Clinical Sarcoma Research
https://www.readbyqxmd.com/read/28479296/the-mammalian-malonyl-coa-synthetase-acsf3-is-required-for-mitochondrial-protein-malonylation-and-metabolic-efficiency
#11
Caitlyn E Bowman, Susana Rodriguez, Ebru S Selen Alpergin, Michelle G Acoba, Liang Zhao, Thomas Hartung, Steven M Claypool, Paul A Watkins, Michael J Wolfgang
Malonyl-coenzyme A (malonyl-CoA) is a central metabolite in mammalian fatty acid biochemistry generated and utilized in the cytoplasm; however, little is known about noncanonical organelle-specific malonyl-CoA metabolism. Intramitochondrial malonyl-CoA is generated by a malonyl-CoA synthetase, ACSF3, which produces malonyl-CoA from malonate, an endogenous competitive inhibitor of succinate dehydrogenase. To determine the metabolic requirement for mitochondrial malonyl-CoA, ACSF3 knockout (KO) cells were generated by CRISPR/Cas-mediated genome editing...
April 26, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/28474529/restoring-of-glucose-metabolism-of-an-engineered-yarrowia-lipolytica-for-succinic-acid-production-via-a-simple-and-efficient-adaptive-evolution-strategy
#12
Xiaofeng Yang, Huaimin Wang, Chong Li, Carol Sze Ki Lin
Succinate dehydrogenase inactivation in Yarrowia lipolytica has been demonstrated for robust succinic acid production, whereas the inefficient glucose metabolism has hindered its practical application. In this study, a simple and efficient adaptive evolution strategy via cell immobilisation was conducted in shake flasks, aiming to restore the glucose metabolism of Y. lipolytica mutant PGC01003. After 21 days with 14 generations evolution, the glucose consumption rate increased to 0.30 g/L/h in YPD medium with 150 g/L initial glucose, while poor yeast growth was observed in such medium intially...
May 5, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28471419/mitochondrial-deficiencies-in-the-predisposition-to-paraganglioma
#13
REVIEW
Charlotte Lussey-Lepoutre, Alexandre Buffet, Anne-Paule Gimenez-Roqueplo, Judith Favier
Paragangliomas and pheochromocytomas are rare neuroendocrine tumours with a very strong genetic component. It is estimated that around 40% of all cases are caused by a germline mutation in one of the 13 predisposing genes identified so far. Half of these inherited cases are intriguingly caused by mutations in genes encoding tricarboxylic acid enzymes, namely SDHA, SDHB, SDHC, SDHD, and SDHAF2 genes, encoding succinate dehydrogenase and its assembly protein, FH encoding fumarate hydratase, and MDH2 encoding malate dehydrogenase...
May 4, 2017: Metabolites
https://www.readbyqxmd.com/read/28462847/breaking-the-ritual-metabolic-cycle-in-order-to-save-acetyl-coa-a-potential-role-for-mitochondrial-humanin-in-t2-bladder-cancer-aggressiveness
#14
Nesreen Nabil Omar, Reham Fathy Tash, Youssef Shoukry, Karim Omar ElSaeed
INTRODUCTION: Cancer cells may exhibit outsourcing of their high energy need in order to avoid the intrinsic mitochondrial apoptosis. Reduced mitochondrial respiration and accumulation of mitochondrial genome mutations are among metabolic transformations in this regard. Mitochondrial humanin (MT-RNR2) is a small peptide with anti-apoptotic activities attributed to binding some pro-apoptotic proteins. AIM OF THE WORK: The current study aims at investigating the expression of mitochondrial humanin in bladder tumor cells and the possible casting of humanin anti-apoptotic action through orchestrating some of the mitochondrial metabolic enzymes...
April 24, 2017: Journal of the Egyptian National Cancer Institute
https://www.readbyqxmd.com/read/28458518/humanin-rescues-cultured-rat-cortical-neurons-from-nmda-induced-toxicity-through-the-alleviation-of-mitochondrial-dysfunction
#15
Ai-Ling Cui, Ying-Hua Zhang, Jian-Zhong Li, Tianbin Song, Xue-Min Liu, Hui Wang, Ce Zhang, Guo-Lin Ma, Hui Zhang, Kefeng Li
N-methyl-D-aspartate (NDMA) receptor-mediated excitotoxicity has been implicated in a variety of pathological situations such as Alzheimer's disease (AD) and Parkinson's disease. However, no effective treatments for the same have been developed so far. Humanin (HN) is a 24-amino acid peptide originally cloned from the brain of patients with AD and it prevents stress-induced cell death in many cells/tissues. In our previous study, HN was found to effectively rescue rat cortical neurons. It is still not clear whether HN protects the neurons through the attenuation of mitochondrial dysfunction...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28456312/characterization-of-boscalid-resistance-conferring-mutations-in-the-sdhb-subunit-of-respiratory-complex-ii-and-impact-on-fitness-and-mycotoxin-production-in-penicillium-expansum-laboratory-strains
#16
Anastasios A Malandrakis, Konstantinos N Vattis, Anastasios N Markoglou, George S Karaoglanidis
Laboratory mutants of Penicillium expansum highly resistant (Rfs: 90 to >500, based on EC50s) to Succinate Dehydrogenase Inhibitors (SDHIs) were isolated after UV-mutagenesis and selection on media containing boscalid. A positive correlation was found between sensitivity of isolates to boscalid and other SDHIs such as isopyrazam and carboxin but not to fungicides affecting other cellular pathways or processes, such as the triazole flusilazole, the phenylpyrrole fludioxonil, the anilinopyrimidine cyprodinil and the benzimidazole benomyl...
May 2017: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/28454689/identification-of-appropriate-reference-genes-for-qpcr-analyses-of-placental-expression-of-slc7a3-and-induction-of-slc5a1-in-porcine-endometrium
#17
Chelsie B Steinhauser, Theodore T Wing, Haijun Gao, Xilong Li, Robert C Burghardt, Guoyao Wu, Fuller W Bazer, Greg A Johnson
INTRODUCTION: Endometria and placentae undergo developmental changes that affect the stability of genes used as references for normalization of qPCR data. We identified genes that are stable within the porcine endometrium and placenta throughout pregnancy, and elucidated the temporal/spatial mRNA localization of the glucose and arginine transporters, solute carrier family (SLC) 5A1 and SLC7A3, respectively. MATERIALS AND METHODS: qPCR was performed for 10 genes within porcine endometria from Days 5, 11, and 15 of the estrous cycle and 11, 15, 25, 40, 60, and 85 of pregnancy; and chorioallantois from Days 30, 35, 45, 50, 60, and 85...
April 2017: Placenta
https://www.readbyqxmd.com/read/28454217/paraganglioma-of-the-organ-of-zuckerkandl-associated-with-a-somatic-hif2%C3%AE-mutation-a-case-report
#18
Ahmad Esmaeel Abdullah, Carole Guerin, Alessio Imperiale, Anne Barlier, Stéphanie Battini, Morgane Pertuit, Philippe Roche, Wassim Essamet, Bernard Vaisse, Karel Pacak, Fréderic Sebag, David Taïeb
Paragangliomas of the organ of Zuckerkandl (OZ-PGL) are rare tumors that, in >70% of cases, occur in association with succinate dehydrogenase complex iron sulfur subunit B (SDHB) or SDHD gene mutations. The aim of the current study was to determine whether a somatic genetic defect in the hypoxia-inducible factor 2α (HIF2α) gene was present in a case of sporadic OZ-PGL. A 32-year-old African female presented with uncontrolled hypertension during the first trimester of pregnancy. A diagnostic hysteroscopy was performed 3 months after delivery, precipitating a hypertensive crisis...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28438637/cloning-and-functional-analysis-of-succinate-dehydrogenase-gene-pssdha-in-phytophthora-sojae
#19
Yuemin Pan, Tao Ye, Zhimou Gao
Succinate dehydrogenase (SDH) is one of the key enzymes of the tricarboxylic acid cycle (TCA cycle) and a proven target of fungicides for true fungi. To explore the roles of the SDHA gene in Phytophthora sojae, we first cloned PsSDHA to construct the PsSDHA silenced expression vector pHAM34-PsSDHA, and then utilized PEG to mediate the P. sojae protoplast transformation experiment. Through transformation screening, we obtained the silenced mutants A1 and A3, which have significant suppressive effect. Further study showed that the hyphae of the silenced mutant strains were shorter and more bifurcated; the growth of the silenced mutants was clearly inhibited in 10% V8 agar medium containing sodium chloride (NaCl), hydrogen peroxide (H2O2) or Congo Red, respectively...
April 21, 2017: Microbial Pathogenesis
https://www.readbyqxmd.com/read/28438610/hyperglycemia-increases-interstitial-cells-of-cajal-via-mapk1-and-mapk3-signaling-to-etv1-and-kit-leading-to-rapid-gastric-emptying
#20
Yujiro Hayashi, Yoshitaka Toyomasu, Siva Arumugam Saravanaperumal, Michael R Bardsley, John A Smestad, Andrea Lorincz, Seth T Eisenman, Gianluca Cipriani, Molly H Nelson Holte, Fatimah J Al Khazal, Sabriya A Syed, Gabriella B Gajdos, Kyoung Moo Choi, Gary J Stoltz, Katie E Miller, Michael L Kendrick, Brian P Rubin, Simon J Gibbons, Adil E Bharucha, David R Linden, Louis James Maher, Gianrico Farrugia, Tamas Ordog
BACKGROUND & AIMS: Depletion of interstitial cells of Cajal (ICCs) is common in diabetic gastroparesis. However, in approximately 20% of patients with diabetes, gastric emptying (GE) is accelerated. GE is also faster in obese individuals, and is associated with increased blood levels of glucose in patients with type 2 diabetes. To understand the fate of ICCs in hyperinsulinemic, hyperglycemic states characterized by rapid GE, we studied mice with mutation of the leptin receptor (Lepr(db/db)), which in our colony had accelerated GE...
April 21, 2017: Gastroenterology
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