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Pyruvate dehydrogenase

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https://www.readbyqxmd.com/read/28543190/effects-of-shrna-mediated-silencing-of-pkm2-gene-on-aerobic-glycolysis-cell-migration-cell-invasion-and-apoptosis-in-colorectal-cancer-cells
#1
Xiao-Ling Yan, Xue-Bin Zhang, Ran Ao, Lin Guan
This study aims to explore the effects of shRNA-mediated silencing on Pyruvate kinase type M2 (PKM2) gene during aerobic glycolysis in colorectal cancer (CRC) cells. CRC tissues and adjacent normal tissues were obtained from 136 patients diagnosed with qRT-PCR, Western blotting and immunohistochemistry (IHC) were performed to detect mRNA and protein expressions of PKM2. CRC cells were divided into a blank, vector and PKM2-shRNA groups. Hexokinase (HK) and PKM2 activity were both determined by glucose-6-phosphate dehydrogenase (G-6-PD) coupled colorimetric assay and enzyme coupling rate method...
May 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28542187/elucidation-of-new-condition-dependent-roles-for-fructose-1-6-bisphosphatase-linked-to-cofactor-balances
#2
Du Toit W P Schabort, Stephanus G Kilian, James C du Preez
The cofactor balances in metabolism is of paramount importance in the design of a metabolic engineering strategy and understanding the regulation of metabolism in general. ATP, NAD+ and NADP+ balances are central players linking the various fluxes in central metabolism as well as biomass formation. NADP+ is especially important in the metabolic engineering of yeasts for xylose fermentation, since NADPH is required by most yeasts in the initial step of xylose utilisation, including the fast-growing Kluyveromyces marxianus...
2017: PloS One
https://www.readbyqxmd.com/read/28539364/integrative-proteomics-and-biochemical-analyses-define-ptc6p-as-the-saccharomyces-cerevisiae-pyruvate-dehydrogenase-phosphatase
#3
Xiao Guo, Natalie M Niemi, Joshua J Coon, Dave J Pagliarini
The pyruvate dehydrogenase complex (PDC) is the primary metabolic checkpoint connecting glycolysis and mitochondrial oxidative phosphorylation, and is important for maintaining cellular and organismal glucose homeostasis. Phosphorylation of the PDC E1 subunit was identified as a key inhibitory modification in bovine tissue approximately 50 years ago, and this regulatory process is now known to be conserved throughout evolution. Although Saccharomyces cerevisiae is a pervasive model organism for investigating cellular metabolism and its regulation by signaling processes, the phosphatase(s) responsible for activating the PDC in S...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28536293/peroxisome-proliferator-activated-receptor-%C3%AE-agonism-attenuates-endotoxaemia-induced-muscle-protein-loss-and-lactate-accumulation-in%C3%A2-rats
#4
Hannah Crossland, Dumitru Constantin-Teodosiu, Sheila Gardiner, Paul Greenhaff
The peroxisome proliferator-activated receptor γ (PPARγ) agonist rosiglitazone (Rosi) appears to provide protection against organ dysfunction during endotoxaemia. We examined the potential benefits of Rosi on skeletal muscle protein maintenance and carbohydrate metabolism during lipopolysaccharide (LPS)-induced endotoxaemia. Sprague-Dawley rats were fed either standard chow (control) or standard chow containing Rosi (8.5±0.1 mg(.)kg(-1.)day(-1)) for two weeks before and during 24 h continuous intravenous infusion of LPS (15 μg(...
May 23, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28530221/micu1-drives-glycolysis-and-chemoresistance-in-ovarian-cancer
#5
Prabir K Chakraborty, Soumyajit Banerjee Mustafi, Xunhao Xiong, Shailendra Kumar Dhar Dwivedi, Vasyl Nesin, Sounik Saha, Min Zhang, Danny Dhanasekaran, Muralidharan Jayaraman, Robert Mannel, Kathleen Moore, Scott McMeekin, Da Yang, Rosemary Zuna, Kai Ding, Leonidas Tsiokas, Resham Bhattacharya, Priyabrata Mukherjee
Cancer cells actively promote aerobic glycolysis to sustain their metabolic requirements through mechanisms not always clear. Here, we demonstrate that the gatekeeper of mitochondrial Ca(2+) uptake, Mitochondrial Calcium Uptake 1 (MICU1/CBARA1) drives aerobic glycolysis in ovarian cancer. We show that MICU1 is overexpressed in a panel of ovarian cancer cell lines and that MICU1 overexpression correlates with poor overall survival (OS). Silencing MICU1 in vitro increases oxygen consumption, decreases lactate production, inhibits clonal growth, migration and invasion of ovarian cancer cells, whereas silencing in vivo inhibits tumour growth, increases cisplatin efficacy and OS...
May 22, 2017: Nature Communications
https://www.readbyqxmd.com/read/28529818/high-protein-fish-oil-diet-prevents-hepatic-steatosis-in-noncnzo10-mice-association-with-diet-genetics-regulated-micro-rnas
#6
Nikhil Adi, Jennipher Adi, Roberta Marques Lassance-Soares, Paul Kurlansky, Hong Yu, Keith A Webster
OBJECTIVE: NONcNZO10 (NZ10) mice are predisposed to obesity and develop type 2 diabetes (T2D) and hepatic steatosis even when maintained on a control diet (CD) of 6% fat. Studies were designed to determine whether this extreme susceptibility phenotype could be alleviated by diet and if so the molecular targets of diet. METHODS: NZ10 and SWR/J (SWR) control mice were fed a CD or a test diet of high protein and fish oil (HPO) for 19 weeks and then analyzed for steatosis, blood chemistry, hepatic gene and micro-RNA expression...
June 2016: Journal of Diabetes & Metabolism
https://www.readbyqxmd.com/read/28527624/understanding-aerobic-anaerobic-metabolism-in-caldibacillus-debilis-through-a-comparison-with-model-organisms
#7
Scott Wushke, Victor Spicer, Xiang Li Zhang, Brian Fristensky, Oleg V Krokhin, David B Levin, Nazim Cicek, Richard Sparling
Caldibacillus debilis GB1 is a facultative anaerobe isolated from a thermophilic aero-tolerant cellulolytic enrichment culture. There is a lack of representative proteomes of facultative anaerobic thermophilic Bacillaceae, exploring aerobic/anaerobic expression. The C. debilis GB1 genome was sequenced and annotated, and the proteome characterized under aerobic and anaerobic conditions while grown on cellobiose. The draft sequence of C. debilis GB1 contains a 3,340,752 bp chromosome and a 5,386 bp plasmid distributed over 49 contigs...
April 13, 2017: Systematic and Applied Microbiology
https://www.readbyqxmd.com/read/28526793/genomic-analysis-of-calderihabitans-maritimus-kkc1-a-thermophilic-hydrogenogenic-carboxydotrophic-bacterium-isolated-from-marine-sediment
#8
Kimiho Omae, Yasuko Yoneda, Yuto Fukuyama, Takashi Yoshida, Yoshihiko Sako
Calderihabitans maritimus KKC1 is a thermophilic hydrogenogenic carboxydotroph isolated from a submerged marine caldera. Here, we describe the de novo sequencing and feature analysis of the C. maritimus KKC1 genome. Genome-based phylogenetic analysis confirmed that C. maritimus KKC1 was most closely related to the genus Moorella, which includes well-studied acetogenic members. Comparative genomic analysis revealed that, like Moorella, C. maritimus KKC1 retained both the CO2-reducing Wood-Ljungdahl pathway and energy-converting hydrogenase-based module activated by reduced ferredoxin, but lacked the HydABC and NfnAB electron bifurcating enzymes and pyruvate:ferredoxin oxidoreductase required for ferredoxin reduction during acetogenic growth...
May 19, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28521863/high-pre-ischemic-fatty-acid-levels-decrease-cardiac-recovery-in-an-isolated-rat-heart-model-of-donation-after-circulatory-death
#9
Petra Niederberger, Emilie Farine, Maria Arnold, Rahel K Wyss, Maria N Sanz, Natalia Méndez-Carmona, Brigitta Gahl, Georg M Fiedler, Thierry P Carrel, Hendrik T Tevaearai Stahel, Sarah L Longnus
RATIONALE: Donation after circulatory death (DCD) could improve cardiac graft availability. However, strategies to optimize cardiac graft recovery remain to be established in DCD; these hearts would be expected to be exposed to high levels of circulatory fat immediately prior to the inevitable period of ischemia prior to procurement. OBJECTIVE: We investigated whether acute exposure to high fat prior to warm, global ischemia affects subsequent hemodynamic and metabolic recovery in an isolated rat heart model of DCD...
June 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/28520713/combining-inferred-regulatory-and-reconstructed-metabolic-networks-enhances-phenotype-prediction-in-yeast
#10
Zhuo Wang, Samuel A Danziger, Benjamin D Heavner, Shuyi Ma, Jennifer J Smith, Song Li, Thurston Herricks, Evangelos Simeonidis, Nitin S Baliga, John D Aitchison, Nathan D Price
Gene regulatory and metabolic network models have been used successfully in many organisms, but inherent differences between them make networks difficult to integrate. Probabilistic Regulation Of Metabolism (PROM) provides a partial solution, but it does not incorporate network inference and underperforms in eukaryotes. We present an Integrated Deduced And Metabolism (IDREAM) method that combines statistically inferred Environment and Gene Regulatory Influence Network (EGRIN) models with the PROM framework to create enhanced metabolic-regulatory network models...
May 17, 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28515908/renal-manifestations-of-primary-mitochondrial-disorders
#11
Josef Finsterer, Fulvio Scorza
The aim of the present review was to summarize and discuss previous findings concerning renal manifestations of primary mitochondrial disorders (MIDs). A literature review was performed using frequently used databases. The study identified that primary MIDs frequently present as mitochondrial multiorgan disorder syndrome (MIMODS) at onset or in the later course of the MID. Occasionally, the kidneys are affected in MIDs. Renal manifestations of MIDs include renal insufficiency, nephrolithiasis, nephrotic syndrome, renal cysts, renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental glomerulosclerosis, tubulointerstitial nephritis, nephrocalcinosis, and benign or malign neoplasms...
May 2017: Biomedical Reports
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
#12
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
#13
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/28510035/ketone-bodies-as-a-possible-adjuvant-to-ketogenic-diet-in-pdhc-deficiency-but-not-in-glut1-deficiency
#14
F Habarou, N Bahi-Buisson, E Lebigot, C Pontoizeau, M T Abi-Warde, A Brassier, K H Le Quan Sang, C Broissand, S Vuillaumier-Barrot, A Roubertie, A Boutron, C Ottolenghi, P de Lonlay
OBJECTIVE: Ketogenic diet is the first line therapy for neurological symptoms associated with pyruvate dehydrogenase deficiency (PDHD) and intractable seizures in a number of disorders, including GLUT1 deficiency syndrome (GLUT1-DS). Because high-fat diet raises serious compliance issues, we investigated if oral L,D-3-hydroxybutyrate administration could be as effective as ketogenic diet in PDHD and GLUT1-DS. METHODS: We designed a partial or total progressive substitution of KD with L,D-3-hydroxybutyrate in three GLUT1-DS and two PDHD patients...
May 17, 2017: JIMD Reports
https://www.readbyqxmd.com/read/28507102/foxo3-pgc-1%C3%AE-signaling-axis-is-essential-for-cancer-stem-cell-properties-of-pancreatic-ductal-adenocarcinoma
#15
Motofumi Kumazoe, Mika Takai, Shun Hiroi, Chieri Takeuchi, Mai Kadomatsu, Takashi Nojiri, Hiroaki Onda, Jaehoon Bae, Yuhui Huang, Kanako Takamatsu, Shuya Yamashita, Kenji Kangawa, Hirofumi Tachibana
In 95% of patients with pancreatic ductal adenocarcinoma (PDAC), recurrence is observed following chemotherapy. Findings from several studies have indicated that cancer stem cells (CSCs) are resistant to anti-cancer agents and may be involved in cancer recurrence and metastasis. The CD44 protein is a major CSC marker, and CD44 also plays an indispensable role in the CSC properties in several cancers, including pancreatic cancer; however, no clinical approach exists to inhibit CD44 activity. Here, we have performed knockin/knock down experiments and we demonstrate that the forkhead box O3 (FOXO3)/liver kinase B1 (LKB1)/AMP-activated protein kinase (AMPK)/PPAR-γ co-activator-1β (PGC- 1β)/pyruvate dehydrogenase -A1 (PDHA1) pathway is essential for CD44 expression and CSC properties...
May 15, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28506930/rewiring-the-reductive-tricarboxylic-acid-pathway-and-l-malate-transport-pathway-of-aspergillus-oryzae-for-overproduction-of-l-malate
#16
Jingjing Liu, Zhipeng Xie, Hyun-Dong Shin, Jianghua Li, Guocheng Du, Jian Chen, Long Liu
Aspergillus oryzae finds wide application in the food, feed, and wine industries, and is an excellent cell factory platform for production of organic acids. In this work, we achieved the overproduction of L-malate by rewiring the reductive tricarboxylic acid (rTCA) pathway and L-malate transport pathway of A. oryzae NRRL 3488. First, overexpression of native pyruvate carboxylase and malate dehydrogenase in the rTCA pathway improved the L-malate titer from 26.1gL(-1) to 42.3gL(-1) in shake flask culture. Then, the oxaloacetate anaplerotic reaction was constructed by heterologous expression of phosphoenolpyruvate carboxykinase and phosphoenolpyruvate carboxylase from Escherichia coli, increasing the L-malate titer to 58...
May 12, 2017: Journal of Biotechnology
https://www.readbyqxmd.com/read/28506882/examination-of-the-superoxide-hydrogen-peroxide-forming-and-quenching-potential-of-mouse-liver-mitochondria
#17
Liam Slade, Julia Chalker, Nidhi Kuksal, Adrian Young, Danielle Gardiner, Ryan J Mailloux
Pyruvate dehydrogenase (PDHC) and α-ketoglutarate dehydrogenase complex (KGDHC) are important sources of reactive oxygen species (ROS). In addition, it has been found that mitochondria can also serve as sinks for cellular hydrogen peroxide (H2O2). However, the ROS forming and quenching capacity of liver mitochondria has never been thoroughly examined. Here, we show that mouse liver mitochondria use catalase, glutathione (GSH), and peroxiredoxin (PRX) systems to quench ROS. Incubation of mitochondria with catalase inhibitor 3-amino-1,2,4-triazole (triazole) induced a significant increase in pyruvate or α-ketoglutarate driven O2(●-)/H2O2 formation...
May 12, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28505407/unique-n-phenylacetylation-and-nrps-with-substrate-promiscuity-for-biosynthesis-of-heptapeptide-variants-jbir-78-and-jbir-95
#18
Kunpei Takeda, Kohei Kemmoku, Yasuharu Satoh, Yasushi Ogasawara, Kazuo Shin-Ya, Tohru Dairi
JBIR-78 (1) and JBIR-95 (2), both of which are heptapeptide derivatives isolated from Kibdelosporangium sp. AK-AA56, have the same amino acid sequences except for the second amino acid; phenylacetic acid (Paa)-L-Val-D-Asp (1)/D-cysteic acid (2)-L-Ala-(3S)-3-hydroxy-D-Leu-Gly-D-Ala-L-Phe. Heterologous expression of the biosynthetic gene cluster including genes encoding non-ribosomal peptide synthetases (NRPS) and in vitro assays with recombinant Orf3, L-cysteic acid synthase homolog, suggested the single A-domain in module 2 activates both L-Asp and L-cysteic acid to yield 1 and 2, respectively, although the substrate specificities of the A-domains of NRPSs are usually strict...
May 15, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28505181/overexpression-of-pyruvate-dehydrogenase-kinase-1-in-retinoblastoma-a-potential-therapeutic-opportunity-for-targeting-vitreous-seeds-and-hypoxic-regions
#19
Swatishree Sradhanjali, Devjyoti Tripathy, Suryasnata Rath, Ruchi Mittal, Mamatha M Reddy
Pyruvate dehydrogenase kinase 1 (PDK1), a key enzyme implicated in metabolic reprogramming of tumors, is induced in several tumors including glioblastoma, breast cancer and melanoma. However, the role played by PDK1 is not studied in retinoblastoma (RB). In this study, we have evaluated the expression of PDK1 in RB clinical samples, and studied its inhibition as a strategy to decrease cell growth and migration. We show that PDK1 is specifically overexpressed in RB patient samples especially in vitreous seeds and hypoxic regions and cell lines compared to control retina using immunohistochemistry and real-time PCR...
2017: PloS One
https://www.readbyqxmd.com/read/28503176/impact-of-autoantibodies-against-glycolytic-enzymes-on-pathogenicity-of-autoimmune-retinopathy-and-other-autoimmune-disorders
#20
REVIEW
Grazyna Adamus
Autoantibodies (AAbs) against glycolytic enzymes: aldolase, α-enolase, glyceraldehyde-3-phosphate dehydrogenase, and pyruvate kinase are prevalent in sera of patients with blinding retinal diseases, such as paraneoplastic [cancer-associated retinopathy (CAR)] and non-paraneoplastic autoimmune retinopathies, as well as in many other autoimmune diseases. CAR is a degenerative disease of the retina characterized by sudden vision loss in patients with cancer and serum anti-retinal AAbs. In this review, we discuss the widespread serum presence of anti-glycolytic enzyme AAbs and their significance in autoimmune diseases...
2017: Frontiers in Immunology
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