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https://www.readbyqxmd.com/read/29304333/tyrosine-1-of-rna-polymerase-ii-ctd-controls-global-termination-of-gene-transcription-in-mammals
#1
Nilay Shah, Muhammad Ahmad Maqbool, Yousra Yahia, Amal Zine El Aabidine, Cyril Esnault, Ignasi Forné, Tim-Michael Decker, David Martin, Roland Schüller, Stefan Krebs, Helmut Blum, Axel Imhof, Dirk Eick, Jean-Christophe Andrau
The carboxy-terminal domain (CTD) of RNA polymerase (Pol) II is composed of a repetition of YSPTSPS heptads and functions as a loading platform for protein complexes that regulate transcription, splicing, and maturation of RNAs. Here, we studied mammalian CTD mutants to analyze the function of tyrosine1 residues in the transcription cycle. Mutation of 3/4 of the tyrosine residues (YFFF mutant) resulted in a massive read-through transcription phenotype in the antisense direction of promoters as well as in the 3' direction several hundred kilobases downstream of genes...
January 4, 2018: Molecular Cell
https://www.readbyqxmd.com/read/29289324/mass-spectrometry-based-analytical-approaches-and-pitfalls-for-toxicometabolomics-of-arsenic-in-mammals-a-tutorial-review
#2
REVIEW
T García-Barrera, G Rodríguez-Moro, B Callejón-Leblic, A Arias-Borrego, J L Gómez-Ariza
The present review focus on the analytical platforms and the workflow for toxicometabolomics with a special emphasis on their strengths and pitfalls presenting as a case study the toxicometabolomics of arsenic in mammals. Although powerful analytical methods and techniques are currently available for metabolomics, the main "bottleneck" is still the absence of unified protocols for sample preparation (e.g. quenching, solvents used) as well as several important factors in toxicometabolomics, which drastically affect the metabolism (e...
February 13, 2018: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29288768/untargeted-metabolic-profiling-reveals-distinct-patterns-of-thermal-sensitivity-in-two-related-notothenioids
#3
Anja Rebelein, Hans-Otto Pörtner, Christian Bock
Antarctic marine ectothermal animals may be affected more than temperate species by rising temperatures due to ongoing climate change. Their specialisation on stable cold temperatures make them vulnerable to even small degrees of warming. Thus, addressing the impacts of warming on Antarctic organisms and identifying their potentially limited capacities to respond is of interest. The objective of the study was to determine changes in metabolite profiles related to temperature acclimation. In a long-term experiment adult fish of two Antarctic sister species Notothenia rossii and Notothenia coriiceps were acclimated to 0 °C and 5 °C for three months...
December 27, 2017: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29281828/the-krebs-cycle-enzyme-isocitrate-dehydrogenase-3a-couples-mitochondrial-metabolism-to-synaptic-transmission
#4
Berrak Ugur, Huan Bao, Michal Stawarski, Lita R Duraine, Zhongyuan Zuo, Yong Qi Lin, G Gregory Neely, Gregory T Macleod, Edwin R Chapman, Hugo J Bellen
Neurotransmission is a tightly regulated Ca2+-dependent process. Upon Ca2+ influx, Synaptotagmin1 (Syt1) promotes fusion of synaptic vesicles (SVs) with the plasma membrane. This requires regulation at multiple levels, but the role of metabolites in SV release is unclear. Here, we uncover a role for isocitrate dehydrogenase 3a (idh3a), a Krebs cycle enzyme, in neurotransmission. Loss of idh3a leads to a reduction of the metabolite, alpha-ketoglutarate (αKG), causing defects in synaptic transmission similar to the loss of syt1...
December 26, 2017: Cell Reports
https://www.readbyqxmd.com/read/29279392/coordinating-carbon-and-nitrogen-metabolic-signaling-through-the-cyanobacterial-global-repressor-ndhr
#5
Yong-Liang Jiang, Xue-Ping Wang, Hui Sun, Shu-Jing Han, Wei-Fang Li, Ning Cui, Gui-Ming Lin, Ju-Yuan Zhang, Wang Cheng, Dong-Dong Cao, Zhi-Yong Zhang, Cheng-Cai Zhang, Yuxing Chen, Cong-Zhao Zhou
The coordination of carbon and nitrogen metabolism is essential for bacteria to adapt to nutritional variations in the environment, but the underlying mechanism remains poorly understood. In autotrophic cyanobacteria, high CO2 levels favor the carboxylase activity of ribulose 1,5 bisphosphate carboxylase/oxygenase (RuBisCO) to produce 3-phosphoglycerate, whereas low CO2 levels promote the oxygenase activity of RuBisCO, leading to 2-phosphoglycolate (2-PG) production. Thus, the 2-PG level is reversely correlated with that of 2-oxoglutarate (2-OG), which accumulates under a high carbon/nitrogen ratio and acts as a nitrogen-starvation signal...
December 26, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29250487/mitochondrial-dysfunction-a-novel-potential-driver-of-epithelial-to-mesenchymal-transition-in-cancer
#6
REVIEW
Flora Guerra, Nicoletta Guaragnella, Arnaldo A Arbini, Cecilia Bucci, Sergio Giannattasio, Loredana Moro
Epithelial-to-mesenchymal transition (EMT) allows epithelial cancer cells to assume mesenchymal features, endowing them with enhanced motility and invasiveness, thus enabling cancer dissemination and metastatic spread. The induction of EMT is orchestrated by EMT-inducing transcription factors that switch on the expression of "mesenchymal" genes and switch off the expression of "epithelial" genes. Mitochondrial dysfunction is a hallmark of cancer and has been associated with progression to a metastatic and drug-resistant phenotype...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29240934/a-peculiar-iclr-family-transcription-factor-regulates-para-hydroxybenzoate-catabolism-in-streptomyces-coelicolor
#7
Rui Zhang, Dana M Lord, Rakhi Bajaj, Wolfgang Peti, Rebecca Page, Jason K Sello
In Streptomyces coelicolor, we identified a para-hydroxybenzoate (PHB) hydroxylase, encoded by gene pobA (SCO3084), which is responsible for conversion of PHB into PCA (protocatechuic acid), a substrate of the β-ketoadipate pathway which yields intermediates of the Krebs cycle. We also found that the transcription of pobA is induced by PHB and is negatively regulated by the product of SCO3209, which we named PobR. The product of this gene is highly unusual in that it is the apparent fusion of two IclR family transcription factors...
December 12, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/29226743/molecular-docking-and-molecular-dynamics-simulations-of-fumarate-hydratase-and-its-mutant-h235n-complexed-with-pyromellitic-acid-and-citrate
#8
S Subasri, Santosh Kumar Chaudhary, K Sekar, Manish Kesherwani, D Velmurugan
Fumarase catalyzes the reversible, stereospecific hydration/dehydration of fumarate to L-malate during the Kreb's cycle. In the crystal structure of the tetrameric fumarase, it was found that some of the active site residues S145, T147, N188 G364 and H235 had water-mediated hydrogen bonding interactions with pyromellitic acid and citrate which help to the protonation state for the conversion of fumarate to malate. When His 235 is mutated with Asn (H235N), water-mediated interactions were lost due to the shifting of active site water molecule by 0...
December 2017: Journal of Bioinformatics and Computational Biology
https://www.readbyqxmd.com/read/29224892/how-glucose-glutamine-and-fatty-acid-metabolism-shape-blood-and-lymph-vessel-development
#9
REVIEW
Laure-Anne Teuwen, Vincent Geldhof, Peter Carmeliet
Recently, endothelial cell metabolism has emerged as an essential driver and regulator of both blood and lymph vessel development. Evidence rapidly builds that metabolism is not only necessary for endothelial cell function, but moreover controls several aspects of the (lymph)-angiogenic process. So far, the best-characterized metabolic pathways to have an impact on angiogenesis are glycolysis, fatty acid oxidation and glutamine metabolism. Glycolysis regulates tip cell behavior by providing ATP, fatty acid oxidation controls stalk cell proliferation by producing nucleotide biomass, and glutamine metabolism is critical for tip and stalk cell dynamics by supporting Krebs cycle anaplerosis, protein production and redox homeostasis, and links to asparagine metabolism...
December 7, 2017: Developmental Biology
https://www.readbyqxmd.com/read/29213095/evolution-of-energy-related-metabolites-in-plasma-from-newborns-with-hypoxic-ischemic-encephalopathy-during-hypothermia-treatment
#10
Ángel Sánchez-Illana, Antonio Núñez-Ramiro, María Cernada, Anna Parra-Llorca, Eva Valverde, Dorotea Blanco, Maria Teresa Moral-Pumarega, Fernando Cabañas, Hector Boix, Antonio Pavon, Mercedes Chaffanel, Isabel Benavente-Fernández, Inés Tofe, Begoña Loureiro, José R Fernández-Lorenzo, Belén Fernández-Colomer, Ana García-Robles, Julia Kuligowski, Máximo Vento
Therapeutic hypothermia (TH) initiated within 6 h from birth is the most effective therapeutic approach for moderate to severe hypoxic-ischemic encephalopathy (HIE). However, underlying mechanisms and effects on the human metabolism are not yet fully understood. This work aims at studying the evolution of several energy related key metabolites in newborns with HIE undergoing TH employing gas chromatography - mass spectrometry. The method was validated following stringent FDA requirements and applied to 194 samples from a subgroup of newborns with HIE (N = 61) enrolled in a multicenter clinical trial (HYPOTOP) for the determination of lactate, pyruvate, ketone bodies and several Krebs cycle metabolites at different sampling time points...
December 6, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29211056/krebs-cycle-metabolites-and-preferential-succinate-oxidation-following-neonatal-hypoxic-ischemic-brain-injury-in-mice
#11
Prateek V Sahni, Jimmy Zhang, Sergey Sosunov, Alexander Galkin, Zoya Niatsetskaya, Anatoly Starkov, Paul S Brookes, Vadim S Ten
BackgroundReverse electron transport (RET) driven by the oxidation of succinate has been proposed as the mechanism of accelerated production of reactive oxygen species (ROS) in post-ischemic mitochondria. However, it remains unclear whether upon reperfusion, mitochondria preferentially oxidase succinate.MethodsNeonatal mice were subjected to Rice-Vannucci model of hypoxic-ischemic brain injury (HI) followed by assessment of Krebs cycle metabolites, mitochondrial substrate preference, and H2O2 generation rate in the ischemic brain...
December 6, 2017: Pediatric Research
https://www.readbyqxmd.com/read/29187824/the-implication-of-pgc-1%C3%AE-on-fatty-acid-transport-across-plasma-and-mitochondrial-membranes-in-the-insulin-sensitive-tissues
#12
REVIEW
Elżbieta Supruniuk, Agnieszka Mikłosz, Adrian Chabowski
PGC-1α coactivator plays a decisive role in the maintenance of lipid balance via engagement in numerous metabolic processes (i.e., Krebs cycle, β-oxidation, oxidative phosphorylation and electron transport chain). It constitutes a link between fatty acids import and their complete oxidation or conversion into bioactive fractions through the coordination of both the expression and subcellular relocation of the proteins involved in fatty acid transmembrane movement. Studies on cell lines and/or animal models highlighted the existence of an upregulation of the total and mitochondrial FAT/CD36, FABPpm and FATPs content in skeletal muscle in response to PGC-1α stimulation...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/29181198/effects-of-long-term-cultivation-on-medium-with-alpha-ketoglutarate-supplementation-on-metabolic-processes-of-saccharomyces-cerevisiae
#13
Nadia Burdyliuk, Maria Bayliak
During last years, alpha-ketoglutarate (AKG), an important intermediate in the Krebs cycle, has been intensively studied as a dietary supplement with stress-protective and potential antiaging effects. Here, we examined the effects of exogenous AKG on metabolic processes and survival of yeast Saccharomyces cerevisiae during long-term cultivation. Growth on AKG had no effect on the total cell number but increased the number of reproductively active cells at the late days of cultivation (from day 7 to day 15)...
2017: Journal of Aging Research
https://www.readbyqxmd.com/read/29181155/comparison-of-the-effect-of-the-aerobic-glycolysis-inhibitor-dichloroacetate-and-of-the-krebs-cycle-inhibitor-lw6-on-cellular-and-humoral-alloimmunity
#14
Theodoros Eleftheriadis, Georgios Pissas, Athanasios Mavropoulos, Vassilios Liakopoulos, Ioannis Stefanidis
Cell metabolism is altered during T-cell and B-cell activation and differentiation. Clarifying the exact metabolic shifts may lead to the development of new immunosuppressive medications. In this study, the effect of the aerobic glycolysis inhibitor dichloroacetate (DCA) and of the Krebs cycle enzyme malate dehydrogenase 2 (MDH2) inhibitor LW6 on T-cell alloimmune clonal expansion and on alloantibody production, was evaluated. T-cell clonal expansion was assessed in two-way mixed lymphocyte reaction (MLR). Humoral alloimmunity was evaluated by the alloantibody production in one-way MLR...
November 2017: Biomedical Reports
https://www.readbyqxmd.com/read/29168615/the-impact-of-rewilding-species-introductions-and-climate-change-on-the-structure-and-function-of-the-yukon-boreal-forest-ecosystem
#15
Rudy Boonstra, Stan Boutin, Thomas S Jung, Charles J Krebs, Shawn Taylor
Community and ecosystem changes are happening in the pristine boreal forest ecosystem of the Yukon for two reasons. First, climate change is affecting the abiotic environment (temperature, rainfall, growing season) and driving changes in plant productivity and predator-prey interactions. Secondly, simultaneously change is occurring because of mammal species reintroductions and rewilding. The key ecological question is the impact these faunal changes will have on trophic dynamics. Primary productivity in the boreal forest is increasing because of climatic warming, but plant species composition is unlikely to change significantly during the next 50-100 years...
November 23, 2017: Integrative Zoology
https://www.readbyqxmd.com/read/29160745/the-unveiling-of-the-warburg-effect-and-the-inscribed-innovative-approach-to-a-radical-non-toxic-anticancer-therapy
#16
Olivia Crociani, Ilaria Marzi, Maria Grazia Cipolleschi, Antonella Mannini, Massimo Contini, Massimo Olivotto
The purpose of this research has been deciphering the Warburg paradox, the biochemical enigma unsolved since 1923. This paradox consists of the aerobic pyruvate conversion to lactate brought about by anaplastic cancer, through the metabolic pathway known as aerobic glycolysis. This pathway implies a heavy energetic waste. We solved the enigma by demonstrating that its specific character, i.e. the forced aerobic lactate exportation, represents a crucial metabolic device to counteract the cytotoxic effect produced by an excess of pyruvate at the connection of glycolysis with the Krebs cycle...
November 21, 2017: Cell Cycle
https://www.readbyqxmd.com/read/29158483/noninvasive-liquid-diet-delivery-of-stable-isotopes-into-mouse-models-for-deep-metabolic-network-tracing
#17
Ramon C Sun, Teresa W-M Fan, Pan Deng, Richard M Higashi, Andrew N Lane, Anh-Thu Le, Timothy L Scott, Qiushi Sun, Marc O Warmoes, Ye Yang
Delivering isotopic tracers for metabolic studies in rodents without overt stress is challenging. Current methods achieve low label enrichment in proteins and lipids. Here, we report noninvasive introduction of (13)C6-glucose via a stress-free, ad libitum liquid diet. Using NMR and ion chromatography-mass spectrometry, we quantify extensive (13)C enrichment in products of glycolysis, the Krebs cycle, the pentose phosphate pathway, nucleobases, UDP-sugars, glycogen, lipids, and proteins in mouse tissues during 12 to 48 h of (13)C6-glucose feeding...
November 21, 2017: Nature Communications
https://www.readbyqxmd.com/read/29155300/mitochondrial-dysfunction-in-obesity
#18
REVIEW
Aline Haas de Mello, Ana Beatriz Costa, Jéssica Della Giustina Engel, Gislaine Tezza Rezin
Obesity leads to various changes in the body. Among them, the existing inflammatory process may lead to an increase in the production of reactive oxygen species (ROS) and cause oxidative stress. Oxidative stress, in turn, can trigger mitochondrial changes, which is called mitochondrial dysfunction. Moreover, excess nutrients supply (as it commonly is the case with obesity) can overwhelm the Krebs cycle and the mitochondrial respiratory chain, causing a mitochondrial dysfunction, and lead to a higher ROS formation...
November 16, 2017: Life Sciences
https://www.readbyqxmd.com/read/29142974/profiling-of-plasma-metabolites-suggests-altered-mitochondrial-fuel-usage-and-remodeling-of-sphingolipid-metabolism-in-individuals-with-type%C3%A2-2-diabetes-and-kidney-disease
#19
Jian-Jun Liu, Sujoy Ghosh, Jean-Paul Kovalik, Jianhong Ching, Hyung Won Choi, Subramaniam Tavintharan, Choon Nam Ong, Chee Fang Sum, Scott A Summers, E Shyong Tai, Su Chi Lim
Introduction: Pathophysiology of diabetic kidney disease (DKD) is incompletely understood. We aim to elucidate metabolic abnormalities associated with DKD in type 2 diabetes mellitus (T2DM) by targeted plasma metabolomics. Methods: A total of 126 T2DM participants with early DKD (urinary albumin-to-creatinine ratio [ACR] 30-299 mg/g and eGFR ≥ 60 ml/min/1.73 m(2)), 154 overt DKD (ACR ≥ 300 mg/g or eGFR < 60 ml/min/1.73 m(2)), and 129 non-DKD T2DM controls (ACR < 30 mg/g and eGFR ≥ 60 ml/min/1...
May 2017: KI Reports
https://www.readbyqxmd.com/read/29133864/effects-of-microgravity-on-osteoblast-mitochondria-a-proteomic-and-metabolomics-profile
#20
Anna Michaletti, Magda Gioia, Umberto Tarantino, Lello Zolla
The response of human primary osteoblasts exposed to simulated microgravity has been investigated and analysis of metabolomic and proteomic profiles demonstrated a prominent dysregulation of mitochondrion homeostasis. Gravitational unloading treatment induced a decrease in mitochondrial proteins, mainly affecting efficiency of the respiratory chain. Metabolomic analysis revealed that microgravity influenced several metabolic pathways; stimulating glycolysis and the pentose phosphate pathways, while the Krebs cycle was interrupted at succinate-fumarate transformation...
November 13, 2017: Scientific Reports
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