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https://www.readbyqxmd.com/read/28300753/krebs-cycle-intermediates-protective-against-oxidative-stress-by-modulating-the-level-of-reactive-oxygen-species-in-neuronal-ht22-cells
#1
Kenta Sawa, Takumi Uematsu, Yusuke Korenaga, Ryuya Hirasawa, Masatoshi Kikuchi, Kyohei Murata, Jian Zhang, Xiaoqing Gai, Kazuichi Sakamoto, Tomoyuki Koyama, Takumi Satoh
Krebs cycle intermediates (KCIs) are reported to function as energy substrates in mitochondria and to exert antioxidants effects on the brain. The present study was designed to identify which KCIs are effective neuroprotective compounds against oxidative stress in neuronal cells. Here we found that pyruvate, oxaloacetate, and α-ketoglutarate, but not lactate, citrate, iso-citrate, succinate, fumarate, or malate, protected HT22 cells against hydrogen peroxide-mediated toxicity. These three intermediates reduced the production of hydrogen peroxide-activated reactive oxygen species, measured in terms of 2',7'-dichlorofluorescein diacetate fluorescence...
March 16, 2017: Antioxidants (Basel, Switzerland)
https://www.readbyqxmd.com/read/28298624/strong-antibiotic-production-is-correlated-with-highly-active-oxidative-metabolism-in-streptomyces-coelicolor-m145
#2
Catherine Esnault, Thierry Dulermo, Aleksey Smirnov, Ahmed Askora, Michelle David, Ariane Deniset-Besseau, Ian-Barry Holland, Marie-Joelle Virolle
The Streptomyces genus is well known for its ability to produce bio-active secondary metabolites of great medical interest. However, the metabolic features accompanying these bio-productions remain to be defined. In this study, the comparison of related model strains producing differing levels of actinorhoddin (ACT), showed that S. lividans, a weak producer, had high TriAcylGlycerol (TAG) content indicative of a glycolytic metabolism. In contrast, the strong producer, S. coelicolor, was characterized by low TAG content, active consumption of its polyphosphate (PolyP) stores and extremely high ATP/ADP ratios...
March 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28292895/diagnosis-of-prostate-cancer-by-desorption-electrospray-ionization-mass-spectrometric-imaging-of-small-metabolites-and-lipids
#3
Shibdas Banerjee, Richard N Zare, Robert J Tibshirani, Christian A Kunder, Rosalie Nolley, Richard Fan, James D Brooks, Geoffrey A Sonn
Accurate identification of prostate cancer in frozen sections at the time of surgery can be challenging, limiting the surgeon's ability to best determine resection margins during prostatectomy. We performed desorption electrospray ionization mass spectrometry imaging (DESI-MSI) on 54 banked human cancerous and normal prostate tissue specimens to investigate the spatial distribution of a wide variety of small metabolites, carbohydrates, and lipids. In contrast to several previous studies, our method included Krebs cycle intermediates (m/z <200), which we found to be highly informative in distinguishing cancer from benign tissue...
March 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28286708/transcriptomic-analysis-reveals-metabolic-switches-and-surface-remodeling-as-key-processes-for-stage-transition-in-trypanosoma-cruzi
#4
Luisa Berná, Maria Laura Chiribao, Gonzalo Greif, Matias Rodriguez, Fernando Alvarez-Valin, Carlos Robello
American trypanosomiasis is a chronic and endemic disease which affects millions of people. Trypanosoma cruzi, its causative agent, has a life cycle that involves complex morphological and functional transitions, as well as a variety of environmental conditions. This requires a tight regulation of gene expression, which is achieved mainly by post-transcriptional regulation. In this work we conducted an RNAseq analysis of the three major life cycle stages of T. cruzi: amastigotes, epimastigotes and trypomastigotes...
2017: PeerJ
https://www.readbyqxmd.com/read/28273139/the-mitochondrial-alternative-oxidase-aox1-is-needed-to-cope-with-respiratory-stress-but-dispensable-for-pathogenic-development-in-ustilago-maydis
#5
Christian A Cárdenas-Monroy, Thomas Pohlmann, Gabriela Piñón-Zárate, Genaro Matus-Ortega, Guadalupe Guerra, Michael Feldbrügge, Juan Pablo Pardo
The mitochondrial alternative oxidase is an important enzyme that allows respiratory activity and the functioning of the Krebs cycle upon disturbance of the respiration chain. It works as a security valve in transferring excessive electrons to oxygen, thereby preventing potential damage by the generation of harmful radicals. A clear biological function, besides the stress response, has so far convincingly only been shown for plants that use the alternative oxidase to generate heat to distribute volatiles. In fungi it was described that the alternative oxidase is needed for pathogenicity...
2017: PloS One
https://www.readbyqxmd.com/read/28261831/hydroxyapatite-nanoparticle-induced-mitochondrial-energy-metabolism-impairment-in-liver-cells-in-vitro-and-in-vivo-studies
#6
Yang Xue, Qingqing Chen, Jiao Sun
Hydroxyapatite nanoparticles (HAP-NPs) have been extensively developed as drug carriers, bone implants, coating materials, etc. in the human body. However, research focusing on the potential side effects of HAP-NPs on the mitochondria-associated energy metabolism in liver cells is lacking. In this study, HAP-NPs with a long diameter of 80 nm and a short diameter of 20 nm were evaluated for their ability to induce mitochondrial energy metabolism dysfunction in vitro and in vivo. In the in vitro system, the buffalo rat hepatocyte (BRL) cell line was directly exposed to the HAP-NPs...
March 6, 2017: Journal of Applied Toxicology: JAT
https://www.readbyqxmd.com/read/28245130/-1-h-nmr-to-evaluate-the-metabolome-of-bronchoalveolar-lavage-fluid-balf-in-bronchiolitis-obliterans-syndrome-bos-toward-the-development-of-a-new-approach-for-biomarker-identification
#7
Carlotta Ciaramelli, Marco Fumagalli, Simona Viglio, Anna Maria Bardoni, Davide Piloni, Federica Meloni, Paolo Iadarola, Cristina Airoldi
This report describes the application of NMR spectroscopy to the profiling of metabolites in bronchoalveolar lavage fluid (BALf) of lung transplant recipients without bronchiolitis obliterans syndrome (BOS) (stable, S, n = 10), and with BOS at different degrees of severity (BOS 0p, n = 10; BOS I, n = 10). Through the fine-tuning of a number of parameters concerning both sample preparation/processing and variations of spectra acquisition modes, an efficient and reproducible protocol was designed for the screening of metabolites in a pulmonary fluid that should reflect the status of airway inflammation/injury...
March 14, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28223908/elevated-urinary-glyphosate-and-clostridia-metabolites-with-altered-dopamine-metabolism-in-triplets-with-autistic-spectrum-disorder-or-suspected-seizure-disorder-a-case-study
#8
William Shaw
CONTEXT: Autism is a neurodevelopmental disorder for which a number of genetic, environmental, and nutritional causes have been proposed. Glyphosate is used widely as a crop desiccant and as an herbicide in fields of genetically modified foods that are glyphosate resistant. Several researchers have proposed that it may be a cause of autism, based on epidemiological data that correlates increased usage of glyphosate with an increased autism rate. OBJECTIVE: The current study was intended to determine if excessive glyphosate was present in the triplets and their parents and to evaluate biochemical findings for the family to determine the potential effects of its presence...
February 2017: Integrative Medicine
https://www.readbyqxmd.com/read/28219702/genetic-alterations-in-krebs-cycle-and-its-impact-on-cancer-pathogenesis
#9
REVIEW
Karishma Sajnani, Farhadul Islam, Robert Anthony Smith, Vinod Gopalan, Alfred King-Yin Lam
Cancer cells exhibit alterations in many cellular processes, including oxygen sensing and energy metabolism. Glycolysis in non-oxygen condition is the main energy production process in cancer rather than mitochondrial respiration as in benign cells. Genetic and epigenetic alterations of Krebs cycle enzymes favour the shift of cancer cells from oxidative phosphorylation to anaerobic glycolysis. Mutations in genes encoding aconitase, isocitrate dehydrogenase, succinate dehydrogenase, fumarate hydratase, and citrate synthase are noted in many cancers...
April 2017: Biochimie
https://www.readbyqxmd.com/read/28216953/therapeutic-potential-of-alpha-ketoglutarate-against-acetaminophen-induced-hepatotoxicity-in-rats
#10
Lalita Mehra, Yasha Hasija, Gaurav Mittal
OBJECTIVE: Alpha-ketoglutarate (α-KG) is a cellular intermediary metabolite of Krebs cycle, involved in energy metabolism, amino acid synthesis, and nitrogen transport. It is available over-the-counter and marketed as a nutritional supplement. There is a growing body of evidence to suggest that dietary α-KG has the potential to maintain cellular redox status and thus can protect various oxidative stress induced disease states. The aim of the present study was to investigate the hepatoprotective role of α-KG in acetaminophen (APAP) induced toxicity in rats...
October 2016: Journal of Pharmacy & Bioallied Sciences
https://www.readbyqxmd.com/read/28208702/the-glutamate-dehydrogenase-pathway-and-its-roles-in-cell-and-tissue-biology-in-health-and-disease
#11
REVIEW
Andreas Plaitakis, Ester Kalef-Ezra, Dimitra Kotzamani, Ioannis Zaganas, Cleanthe Spanaki
Glutamate dehydrogenase (GDH) is a hexameric enzyme that catalyzes the reversible conversion of glutamate to α-ketoglutarate and ammonia while reducing NAD(P)⁺ to NAD(P)H. It is found in all living organisms serving both catabolic and anabolic reactions. In mammalian tissues, oxidative deamination of glutamate via GDH generates α-ketoglutarate, which is metabolized by the Krebs cycle, leading to the synthesis of ATP. In addition, the GDH pathway is linked to diverse cellular processes, including ammonia metabolism, acid-base equilibrium, redox homeostasis (via formation of fumarate), lipid biosynthesis (via oxidative generation of citrate), and lactate production...
February 8, 2017: Biology
https://www.readbyqxmd.com/read/28168164/vdac-tubulin-an-anti-warburg-pro-oxidant-switch
#12
REVIEW
Eduardo N Maldonado
Aerobic enhanced glycolysis characterizes the Warburg phenotype. In cancer cells, suppression of mitochondrial metabolism contributes to maintain a low ATP/ADP ratio that favors glycolysis. We propose that the voltage-dependent anion channel (VDAC) located in the mitochondrial outer membrane is a metabolic link between glycolysis and oxidative phosphorylation in the Warburg phenotype. Most metabolites including respiratory substrates, ADP, and Pi enter mitochondria only through VDAC. Oxidation of respiratory substrates in the Krebs cycle generates NADH that enters the electron transport chain (ETC) to generate a proton motive force utilized to generate ATP and to maintain mitochondrial membrane potential (ΔΨ)...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28166989/dose-dependent-inhibition-of-uterine-contractility-by-nitric-oxide-a-potential-mechanism-underlying-persistent-breeding-induced-endometritis-in-the-mare
#13
Firdous A Khan, Tracey S Chenier, Coral L Murrant, Robert A Foster, Joanne Hewson, Elizabeth L Scholtz
Nitric oxide (NO) may have a role in persistent breeding-induced endometritis in mares through an inhibitory effect on uterine contractility. The objectives of this study were to test the effect of NO on spontaneous uterine contractility in-vitro and to evaluate whether this effect varied between the longitudinal and circular muscle layers of the uterus. Reproductive tracts were collected from eight euthanized non-pregnant mares (age 4-19 years; body weight 405-530 kg). Transrectal examination of the reproductive tract was performed before euthanasia to evaluate stage of the estrous cycle and presence of any apparent abnormality...
March 1, 2017: Theriogenology
https://www.readbyqxmd.com/read/28163219/probing-the-metabolic-phenotype-of-breast-cancer-cells-by-multiple-tracer-stable-isotope-resolved-metabolomics
#14
Andrew N Lane, Julie Tan, Yali Wang, Jun Yan, Richard M Higashi, Teresa W-M Fan
Breast cancers vary by their origin and specific set of genetic lesions, which gives rise to distinct phenotypes and differential response to targeted and untargeted chemotherapies. To explore the functional differences of different breast cell types, we performed Stable Isotope Resolved Metabolomics (SIRM) studies of one primary breast (HMEC) and three breast cancer cells (MCF-7, MDAMB-231, and ZR75-1) having distinct genotypes and growth characteristics, using (13)C6-glucose, (13)C-1+2-glucose, (13)C5,(15)N2-Gln, (13)C3-glycerol, and (13)C8-octanoate as tracers...
February 2, 2017: Metabolic Engineering
https://www.readbyqxmd.com/read/28153450/tailored-liquid-chromatography-mass-spectrometry-analysis-improves-the-coverage-of-the-intracellular-metabolome-of-heparg-cells
#15
Matthias Cuykx, Noelia Negreira, Charlie Beirnaert, Nele Van den Eede, Robim Rodrigues, Tamara Vanhaecke, Kris Laukens, Adrian Covaci
Metabolomics protocols are often combined with Liquid Chromatography-Mass Spectrometry (LC-MS) using mostly reversed phase chromatography coupled to accurate mass spectrometry, e.g. quadrupole time-of-flight (QTOF) mass spectrometers to measure as many metabolites as possible. In this study, we optimised the LC-MS separation of cell extracts after fractionation in polar and non-polar fractions. Both phases were analysed separately in a tailored approach in four different runs (two for the non-polar and two for the polar-fraction), each of them specifically adapted to improve the separation of the metabolites present in the extract...
March 3, 2017: Journal of Chromatography. A
https://www.readbyqxmd.com/read/28153317/optimizing-2d-gas-chromatography-mass-spectrometry-for-robust-tissue-serum-and-urine-metabolite-profiling
#16
Zhanru Yu, Honglei Huang, Alexander Reim, Philip D Charles, Alan Northage, Dianne Jackson, Ian Parry, Benedikt M Kessler
Two-dimensional gas chromatography mass spectrometry (GCxGC-MS) is utilized to an increasing extent in biomedical metabolomics. Here, we established and adapted metabolite extraction and derivatization protocols for cell/tissue biopsy, serum and urine samples according to their individual properties. GCxGC-MS analysis revealed detection of ~600 molecular features from which 165 were characterized representing different classes such as amino acids, fatty acids, lipids, carbohydrates, nucleotides and small polar components of glycolysis and the Krebs cycle using electron impact (EI) spectrum matching and validation using external standard compounds...
April 1, 2017: Talanta
https://www.readbyqxmd.com/read/28139779/the-%C3%AE-and-%C3%AE-subunits-play-distinct-functional-roles-in-the-%C3%AE-2%C3%AE-%C3%AE-heterotetramer-of-human-nad-dependent-isocitrate-dehydrogenase
#17
Tengfei Ma, Yingjie Peng, Wei Huang, Yabing Liu, Jianping Ding
Human NAD-dependent isocitrate dehydrogenase existing as the α2βγ heterotetramer, catalyzes the decarboxylation of isocitrate into α-ketoglutarate in the Krebs cycle, and is allosterically regulated by citrate, ADP and ATP. To explore the functional roles of the regulatory β and γ subunits, we systematically characterized the enzymatic properties of the holoenzyme and the composing αβ and αγ heterodimers in the absence and presence of regulators. The biochemical and mutagenesis data show that αβ and αγ alone have considerable basal activity but the full activity of α2βγ requires the assembly and cooperative function of both heterodimers...
January 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28127420/permanent-draft-genome-of-thiobacillus-thioparus-dsm-505-t-an-obligately-chemolithoautotrophic-member-of-the-betaproteobacteria
#18
Lee P Hutt, Marcel Huntemann, Alicia Clum, Manoj Pillay, Krishnaveni Palaniappan, Neha Varghese, Natalia Mikhailova, Dimitrios Stamatis, Tatiparthi Reddy, Chris Daum, Nicole Shapiro, Natalia Ivanova, Nikos Kyrpides, Tanja Woyke, Rich Boden
Thiobacillus thioparus DSM 505(T) is one of first two isolated strains of inorganic sulfur-oxidising Bacteria. The original strain of T. thioparus was lost almost 100 years ago and the working type strain is Culture C(T) (=DSM 505(T) = ATCC 8158(T)) isolated by Starkey in 1934 from agricultural soil at Rutgers University, New Jersey, USA. It is an obligate chemolithoautotroph that conserves energy from the oxidation of reduced inorganic sulfur compounds using the Kelly-Trudinger pathway and uses it to fix carbon dioxide It is not capable of heterotrophic or mixotrophic growth...
2017: Standards in Genomic Sciences
https://www.readbyqxmd.com/read/28126513/inhibition-of-the-respiratory-chain-reactions-in-denitrifying-ebpr-biomass-under-simultaneous-presence-of-acetate-and-electron-acceptor
#19
Ilias Zafiriadis, Anastasios G Kapagiannidis, Spyridon Ntougias, Alexander Aivasidis
In this study, the deterioration of the typical EBPR (Enhanced Biological Phosphorus Removal) process due to the simultaneous presence of electron donor (external substrate) and electron acceptor (oxygen or nitrate) was investigated by using a PAOs (Polyphosphate Accumulating Organisms)-enriched biomass grown in a modified DEPHANOX system. Intracellular and extracellular constituents were monitored in batch tests under different electron donor and acceptor conditions and specific oxygen and nitrogen uptake rates were evaluated...
May 25, 2017: New Biotechnology
https://www.readbyqxmd.com/read/28116532/reversible-stress-softening-in-layered-rat-esophagus-in-vitro-after-potassium-chloride-activation
#20
Hongbo Jiang, Donghua Liao, Jingbo Zhao, Guixue Wang, Hans Gregersen
Significant stress softening recovery after potassium chloride (KCl) administration was previously demonstrated in the intact rat esophageal wall. The aim of this study is to investigate the effect of KCl activation on stress softening recovery in the separated mucosa-submucosa layer and muscle layer of rat esophagus. Three series of loading-unloading distensions were carried out on 10 rat esophagi where the two separated layers were distended at luminal pressure levels 0.5, 1.0 and 2.0 kPa. Numerous distension cycles were done in [Formula: see text]-free Krebs solution before and after activation with KCl (110 mmol) for 3 min in calcium-containing media...
January 23, 2017: Biomechanics and Modeling in Mechanobiology
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