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Pyruvate dehydrogenase

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https://www.readbyqxmd.com/read/29330215/mir-195-regulates-metabolism-in-failing-myocardium-via-alterations-in-sirt3-expression-and-mitochondrial-protein-acetylation
#1
Xiaokan Zhang, Ruiping Ji, Xianghai Liao, Estibaliz Castillero, Peter J Kennel, Danielle L Brunjes, Marcus Franz, Sven Möbius-Winkler, Konstantinos Drosatos, Isaac George, Emily I Chen, Paolo C Colombo, P Christian Schulze
Background -Heart failure (HF) leads to mitochondrial dysfunction and metabolic abnormalities of the failing myocardium coupled with an energy-depleted state and cardiac remodeling. The mitochondrial deacetylase sirtuin 3 (SIRT3) plays a pivotal role in the maintenance of mitochondrial function through regulating the mitochondrial acetylome. Interestingly, unique cardiac and systemic miRNAs have been shown to play an important role in cardiac remodeling by modulating key signaling elements in the myocardium...
January 12, 2018: Circulation
https://www.readbyqxmd.com/read/29319912/transcriptomics-in-the-wild-hibernation-physiology-in-free-ranging-dwarf-lemurs
#2
Sheena L Faherty, José Luis Villanueva-Cañas, Marina B Blanco, Mar M Albà, Anne D Yoder
Hibernation is an adaptive strategy some mammals use to survive highly seasonal or unpredictable environments. We present the first investigation on the transcriptomics of hibernation in a natural population of primate hibernators: Crossley's dwarf lemurs (Cheirogaleus crossleyi). Using capture-mark-recapture techniques to track the same animals over a period of seven months in Madagascar, we used RNA-seq to compare gene expression profiles in white adipose tissue (WAT) during three distinct physiological states...
January 10, 2018: Molecular Ecology
https://www.readbyqxmd.com/read/29315780/high-resolution-hyperpolarized-13-c-mrsi-using-spice-at-9-4t
#3
Hansol Lee, Jae Eun Song, Jaewook Shin, Eunhae Joe, Chan Gyu Joo, Young-Suk Choi, Ho-Taek Song, Dong-Hyun Kim
PURPOSE: To test the feasibility of using the SPICE (SPectroscopic Imaging by exploiting spatiospectral CorrElation) technique, which uses the partial separability of spectroscopic data, for high resolution hyperpolarized (HP) 13 C spectroscopic imaging. METHODS: Numerical simulations were performed to investigate the impact of transient HP signals on SPICE reconstruction. Furthermore, spectroscopic imaging exams from SPICE and conventional EPSI (echo-planar spectroscopic imaging) were simulated for comparison...
January 8, 2018: Magnetic Resonance in Medicine: Official Journal of the Society of Magnetic Resonance in Medicine
https://www.readbyqxmd.com/read/29310734/differential-methylation-of-insulin-like-growth-factor-2-in-offspring-of-physically-active-pregnant-women
#4
M R Marshall, N Paneth, J A Gerlach, L M Mudd, L Biery, D P Ferguson, J M Pivarnik
Several studies have suggested that maternal lifestyle during pregnancy may influence long-term health of offspring by altering the offspring epigenome. Whether maternal leisure-time physical activity (LTPA) during pregnancy might have this effect is unknown. The purpose of this study was to determine the relationship between maternal LTPA during pregnancy and offspring DNA methylation. Participants were recruited from the Archive for Research on Child Health study. At enrollment, participants' demographic information and self-reported LTPA during pregnancy were determined...
January 9, 2018: Journal of Developmental Origins of Health and Disease
https://www.readbyqxmd.com/read/29303786/aerobic-glycolysis-in-amyotrophic-lateral-sclerosis-and-huntington-s-disease
#5
REVIEW
Alexandre Vallée, Yves Lecarpentier, Rémy Guillevin, Jean-Noël Vallée
Neurodegenerative cells are the sites of numerous metabolic and energetic abnormalities with abnormalities in energy production. Energy is the primary determinant of neuronal viability. In neurodegenerative cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In amyotrophic lateral sclerosis (ALS) and Huntington's disease (HD), WNT/β-catenin pathway is upregulated. We focused this review on the hypothesis of aerobic glycolysis stimulated by the upregulation of WNT/β-catenin pathway in ALS and HD...
January 5, 2018: Reviews in the Neurosciences
https://www.readbyqxmd.com/read/29303599/proteomic-analysis-of-peroxynitrite-induced-protein-nitration-in-isolated-beef-heart-mitochondria
#6
M Kohutiar, A Eckhardt, I Mikšík, P Šantorová, J Wilhelm
Mitochondria are exposed to reactive nitrogen species under physiological conditions and even more under several pathologic states. In order to reveal the mechanism of these processes we studied the effects of peroxynitrite on isolated beef heart mitochondria in vitro. Peroxynitrite has the potential to nitrate protein tyrosine moieties, break the peptide bond, and eventually release the membrane proteins into the solution. All these effects were found in our experiments. Mitochondrial proteins were resolved by 2D electrophoresis and the protein nitration was detected by immunochemical methods and by nano LC-MS/MS...
January 5, 2018: Physiological Research
https://www.readbyqxmd.com/read/29301853/-pro-renin-receptor-inhibition-reprograms-hepatic-lipid-metabolism-and-protects-mice-from-diet-induced-obesity-and-hepatosteatosis
#7
Liwei Ren, Yuan Sun, Hong Lu, Dien Ye, Lijuan Han, Na Wang, Alan Daugherty, Furong Li, Miaomiao Wang, Fengting Su, Wenjun Tao, Jie Sun, Noam Zelcer, Adam E Mullick, Ah J Danser, Yizhou Jiang, Yongcheng He, Xiongzhong Ruan, Xifeng Lu
Rationale: An elevated level of plasma low-density lipoprotein (LDL) is an established risk factor for cardiovascular disease. Recently, we reported that the (pro)renin receptor ([P]RR) regulates LDL metabolism in vitro via the LDL receptor (LDLR) and SORT1, independently of the renin-angiotensin system. Objective: To investigate the physiological role of [P]RR in lipid metabolism in vivo. Methods and Results: We used N-Acetylgalactosamine (GalNAc) modified antisense oligonucleotides (ASO) to specifically inhibit hepatic [P]RR expression in C57BL/6J mice, and studied the consequences this has on lipid metabolism...
January 4, 2018: Circulation Research
https://www.readbyqxmd.com/read/29301575/warburg-effect-hypothesis-in-autism-spectrum-disorders
#8
REVIEW
Alexandre Vallée, Jean-Noël Vallée
Autism spectrum disorder (ASD) is a neurodevelopmental disease which is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. In altered cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In ASD, the canonical WNT/β-catenin pathway is upregulated. We focus this review on the hypothesis of Warburg effect stimulated by the overexpression of the canonical WNT/β-catenin pathway in ASD. Upregulation of WNT/β-catenin pathway induces aerobic glycolysis, named Warburg effect, through activation of glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactate dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH)...
January 4, 2018: Molecular Brain
https://www.readbyqxmd.com/read/29299540/development-of-a-fluorescent-capillary-biosensor-based-on-self-assembled-aunp-ldh-for-micro-volume-intracellular-pyruvate
#9
Ya-Xiong Luo, Qiao-Jing Li, Lang Zhou, Yong-Sheng Li, Xiu-Feng Gao
Herein, a fluorescent capillary biosensor was developed for quantifying micro-volume intracellular pyruvate (PA), in which AuNPs and lactate dehydrogenase (LDH) were modified on the inner surface of an amination capillary (20 μL) via a self-assembly technique. The PA concentration was quantified by the change in the value of the fluorescence of NADH after sucking a mixed solution of the sample and NADH into the biosensor. This study investigated factors including the degree of protonation of the amino groups on the surface of the capillary, the AuNP concentration and time for self-assembly, the activity concentration and time for the LDH self-assembly, the flow rate and acidity for LDH immobilization, pH, temperature, and reaction time for the NADH/PA/LDH reaction system...
January 4, 2018: Analyst
https://www.readbyqxmd.com/read/29299212/risk-factors-of-mortality-due-to-acute-opium-poisoning-a-report-from-the-largest-intoxication-referral-center-in-iran
#10
Sahar Rismantab-Sani, Babak Soltani, Siamak Soltani, Azadeh Memarian
Background: Studies have shown that Iran has a high rate of opiate abuse and the most prevalently used is opium. This study was aimed to evaluate risk factors in patients with acute opium intoxication who referred to Loghman Hakim Hospital, Tehran, Iran, in 2011. Methods: A total number of 383 patients with acute opium overdose, who were referred to the Emergency Department of Loghman Hakim Hospital in Tehran during 2011, were enrolled into this descriptive, cross-sectional study...
April 2017: Addiction & Health
https://www.readbyqxmd.com/read/29298056/full-enyzme-complex-simulation-interactions-in-human-pyruvate-dehydrogenase-complex
#11
Samira Hezaveh, An-Ping Zeng, Uwe Jandt
The pyruvate dehydrogenase complex (PDC) is a large macromolecular machine consisting of dozens of interacting enzymes that are connected and regulated by highly flexible domains, also called swinging arms. The overall structure and function of these domains and how they organize the complex function is rarely elucidated yet. This lack of structural and dynamic understanding is frequently observed in multi domain enzymatic complexes. Here we present the first full and dynamic structural model of full human PDC (hPDC), including the linking arms binding to the surrounding E1 and E3 enzymes via their binding domains with variable stoichiometries...
January 3, 2018: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29285418/pdk4-deficiency-induces-intrinsic-apoptosis-in-response-to-starvation-in-fibroblasts-from-doberman-pinschers-with-dilated-cardiomyopathy
#12
Kathryn Taggart, Amara Estrada, Patrick Thompson, Francisco Lourenco, Sara Kirmani, Silveli Suzuki-Hatano, Christina A Pacak
The Doberman pinscher (DP) canine breed displays a high incidence of idiopathic, nonischemic dilated cardiomyopathy (DCM) with increased mortality. A common mutation in DPs is a splice site deletion in the pyruvate dehydrogenase kinase 4 (PDK4) gene that shows a positive correlation with DCM development. PDK4, a vital mitochondrial protein, controls the switch between glycolysis and oxidative phosphorylation based upon nutrient availability. It is likely, although unproven, that DPs with the PDK4 mutation are unable to switch to oxidative phosphorylation during periods of low nutrient availability, and thus are highly susceptible to mitochondrial-mediated apoptosis...
2017: BioResearch Open Access
https://www.readbyqxmd.com/read/29274570/characterization-of-the-impact-of-glutaredoxin-2-grx2-deficiency-on-superoxide-hydrogen-peroxide-release-from-cardiac-and-liver-mitochondria
#13
Julia Chalker, Danielle Gardiner, Nidhi Kuksal, Ryan J Mailloux
Mitochondria are critical sources of hydrogen peroxide (H2O2), an important secondary messenger in mammalian cells. Recent work has shown that O2•-/H2O2 emission from individual sites of production in mitochondria is regulated by protein S-glutathionylation. Here, we conducted the first examination of O2•-/H2O2 release rates from cardiac and liver mitochondria isolated from mice deficient for glutaredoxin-2 (GRX2), a matrix-associated thiol oxidoreductase that facilitates the S-glutathionylation and deglutathionylation of proteins...
December 14, 2017: Redox Biology
https://www.readbyqxmd.com/read/29261292/haloacetic-acid-water-disinfection-by-products-affect-pyruvate-dehydrogenase-activity-and-disrupt-cellular-metabolism
#14
Azra Dad, Clara Hyunhee Jeong, Elizabeth D Wagner, Michael J Plewa
The disinfection of drinking water has been a major public health achievement. However, haloacetic acids (HAAs), generated as by-products of water disinfection, are cytotoxic, genotoxic, mutagenic, carcinogenic and teratogenic. Previous studies of monoHAA-induced genotoxicity and cell stress demonstrated that the toxicity was due to inhibition of glyceraldehyde-3-phosphate dehydrogenase (GAPDH) leading to disruption of cellular metabolism and energy homeostasis. DiHAAs and triHAAs are also produced during water disinfection, and whether they share mechanisms of action with monoHAAs is unknown...
December 20, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29247844/strategies-of-biochemical-adaptation-for-hibernation-in-a-south-american-marsupial-dromiciops-gliroides-4-regulation-of-pyruvate-dehydrogenase-complex-and-metabolic-fuel-selection
#15
Sanoji Wijenayake, Bryan E Luu, Jing Zhang, Shannon N Tessier, Julian F Quintero-Galvis, Juan Diego Gaitán-Espitia, Roberto F Nespolo, Kenneth B Storey
Mammalian hibernation is characterized by extensive adjustments to metabolism that typically include suppression of carbohydrate catabolism and a switch to triglycerides as the primary fuel during torpor. A crucial locus of control in this process is the pyruvate dehydrogenase complex that gates carbohydrate entry into the tricarboxylic acid cycle. Within the complex, the E1 enzyme pyruvate dehydrogenase (PDH) is the main regulatory site and is subject to inhibitory phosphorylation at three serine residues (S232, S293, S300)...
December 13, 2017: Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/29241575/dietary-supplementation-with-myo-inositol-reduces-hepatic-triglyceride-accumulation-and-expression-of-both-fructolytic-and-lipogenic-genes-in-rats-fed-a-high-fructose-diet
#16
Masaya Shimada, Masato Hibino, Anna Takeshita
Excessive fructose ingestion drastically enhances hepatic lipid accumulation. The most prominent form of inositol-myo-inositol (MI)-remarkably reduces high sucrose-induced hepatic triglyceride (TG) accumulation. Because MI is a major and strong lipotrope, we hypothesized in this study that MI improves fatty liver more induced by excessive ingestion of fructose than sucrose. Rats were fed a high-glucose diet (HGD), a high-fructose diet (HFD), or an HFD supplemented with 0.2% MI for 12 days. Hepatic levels of TG and mRNAs for fructolysis (ketohexokinase and aldolase B), lipogenesis (pyruvate kinase, liver, and RBC; glucose-6-phosphate dehydrogenase; acetyl-CoA carboxylase alpha; fatty acid synthase; and stearoyl-CoA desaturase 1), and a key transcription factor for lipogenesis-carbohydrate-responsive element-binding protein-were significantly increased in the HFD group compared with the HGD group, and the increase was markedly decreased by MI supplementation...
November 2017: Nutrition Research
https://www.readbyqxmd.com/read/29236080/three-dimensional-analysis-of-the-interactions-between-hldh5-and-its-inhibitors
#17
REVIEW
Giulio Poli, Carlotta Granchi, Mohamed Aissaoui, Filippo Minutolo, Tiziano Tuccinardi
Inhibitors of human lactate dehydrogenase (hLDH5)-the enzyme responsible for the conversion of pyruvate to lactate coupled with oxidation of NADH to NAD⁺-are promising therapeutic agents against cancer because this enzyme is generally found to be overexpressed in most invasive cancer cells and is linked to their vitality especially under hypoxic conditions. Consequently, significant efforts have been made for the identification of small-molecule hLDH5 inhibitors displaying high inhibitory potencies. X-ray structure of hLDH5 complexes as well as molecular modeling studies contribute to identify and explain the main binding modes of hLDH5 inhibitors reported in literature...
December 13, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29235509/in-vivo-metabolic-imaging-of-traumatic-brain-injury
#18
Caroline Guglielmetti, Austin Chou, Karen Krukowski, Chloe Najac, Xi Feng, Lara-Kirstie Riparip, Susanna Rosi, Myriam M Chaumeil
Complex alterations in cerebral energetic metabolism arise after traumatic brain injury (TBI). To date, methods allowing for metabolic evaluation are highly invasive, limiting our understanding of metabolic impairments associated with TBI pathogenesis. We investigated whether 13C MRSI of hyperpolarized (HP) [1-13C] pyruvate, a non-invasive metabolic imaging method, could detect metabolic changes in controlled cortical injury (CCI) mice (n = 57). Our results show that HP [1-13C] lactate-to-pyruvate ratios were increased in the injured cortex at acute (12/24 hours) and sub-acute (7 days) time points after injury, in line with decreased pyruvate dehydrogenase (PDH) activity, suggesting impairment of the oxidative phosphorylation pathway...
December 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29234670/mitochondrial-energy-metabolism-is-required-for-lifespan-extension-by-the-spastic-paraplegia-associated-protein-spartin
#19
Julia Ring, Patrick Rockenfeller, Claudia Abraham, Jelena Tadic, Michael Poglitsch, Katherina Schimmel, Julia Westermayer, Simon Schauer, Bettina Achleitner, Christa Schimpel, Barbara Moitzi, Gerald N Rechberger, Stephan J Sigrist, Didac Carmona-Gutierrez, Guido Kroemer, Sabrina Büttner, Tobias Eisenberg, Frank Madeo
Hereditary spastic paraplegias, a group of neurodegenerative disorders, can be caused by loss-of-function mutations in the protein spartin. However, the physiological role of spartin remains largely elusive. Here we show that heterologous expression of human or Drosophila spartin extends chronological lifespan of yeast, reducing age-associated ROS production, apoptosis, and necrosis. We demonstrate that spartin localizes to the proximity of mitochondria and physically interacts with proteins related to mitochondrial and respiratory metabolism...
November 30, 2017: Microbial Cell
https://www.readbyqxmd.com/read/29234335/metabolite-profiling-of-wheat-seedlings-induced-by-chitosan-revelation-of-the-enhanced-carbon-and-nitrogen-metabolism
#20
Xiaoqian Zhang, Kecheng Li, Ronge Xing, Song Liu, Pengcheng Li
Chitosan plays an important role in regulating growth and eliciting defense in many plant species. However, the exact metabolic response of plants to chitosan is still not clear. The present study performed an integrative analysis of metabolite profiles in chitosan-treated wheat seedlings and further investigated the response of enzyme activities and transcript expression related to the primary carbon (C) and nitrogen (N) metabolism. Metabolite profiling revealed that chitosan could induce significant difference of organic acids, sugars and amino acids in leaves of wheat seedlings...
2017: Frontiers in Plant Science
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