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https://www.readbyqxmd.com/read/28435050/the-human-krebs-cycle-2-oxoglutarate-dehydrogenase-complex-creates-an-additional-source-of-superoxide-hydrogen-peroxide-from-2-oxoadipate-as-alternative-substrate
#1
Natalia S Nemeria, Gary Gerfen, Elena Guevara, Pradeep Reddy Nareddy, Michal Szostak, Frank Jordan
Recently, we reported that the human 2-oxoglutarate dehydrogenase (hE1o) component of the 2-oxoglutarate dehydrogenase complex (OGDHc) could produce the reactive oxygen species superoxide and hydrogen peroxide (detected by chemical means) from its substrate 2-oxoglutarate (OG), most likely concurrently with one-electron oxidation by dioxygen of the thiamin diphosphate (ThDP)-derived enamine intermediate to a C2α-centered radical (detected by Electron Paramagnetic Resonance) [Nemeria et al., 2014; Ambrus et al...
April 20, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28429330/growth-kinetics-fatty-acid-composition-and-metabolic-activity-changes-of-crypthecodinium-cohnii-under-different-nitrogen-source-and-concentration
#2
Waseem Safdar, Muhammad Shamoon, Xinyi Zan, Junaid Haider, Hafiz Rizwan Sharif, Muhammad Shoaib, Yuanda Song
The effect of varying concentrations of the nitrogen source on the growth kinetics, lipid accumulation, lipid and DHA productivity, and fatty acid composition of C. cohnii was elucidated. Growth of C. cohnii was in three distinct growth stages: cell growth, lipid accumulation and a final lipid turnover stage. Most of lipids were accumulated in lipid accumulation stage (48-120 h) though, slow growth rate was observed during this stage. NaNO3 supported significantly higher lipid content (26.9% of DCW), DHA content (0...
December 2017: AMB Express
https://www.readbyqxmd.com/read/28424233/cluh-couples-mitochondrial-distribution-to-the-energetic-and-metabolic-status
#3
Jamal Wakim, David Goudenege, Rodolphe Perrot, Naig Gueguen, Valerie Desquiret-Dumas, Juan Manuel Chao de la Barca, Ilaria Dalla Rosa, Florence Manero, Morgane Le Mao, Stephanie Chupin, Arnaud Chevrollier, Vincent Procaccio, Dominique Bonneau, David C Logan, Pascal Reynier, Guy Lenaers, Salim Khiati
Mitochondrial dynamics and distribution are critical in supplying ATP in response to energy demand. CLUH is a protein involved in mitochondrial distribution, whose dysfunction leads to mitochondrial clustering, the metabolic consequences of which remain unknown. To gain insight into the role of CLUH on mitochondrial energy production and cellular metabolism, we have generated CLUH knockout cells using CRISPR/Cas9. Mitochondrial clustering was associated with a smaller cell size, and with decreased abundance of respiratory complexes, resulting in OXPHOS defects...
April 19, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28423352/prospective-serum-metabolomic-profile-of-prostate-cancer-by-size-and-extent-of-primary-tumor
#4
Jiaqi Huang, Alison M Mondul, Stephanie J Weinstein, Edward D Karoly, Joshua N Sampson, Demetrius Albanes
Two recent investigations found serum lipid and energy metabolites related to aggressive prostate cancer up to 20 years prior to diagnosis. To elucidate whether those metabolomic profiles represent etiologic or tumor biomarker signals, we prospectively examined serum metabolites of prostate cancer cases by size and extent of primary tumors in a nested case-control analysis in the ATBC Study cohort that compared cases diagnosed with T2 (n = 71), T3 (n = 51), or T4 (n = 15) disease to controls (n = 200). Time from fasting serum collection to diagnosis averaged 10 years (range 1-20)...
April 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419197/inhibition-of-sarcolemmal-fat-cd36-by-sulfo-n-succinimidyl-oleate-rapidly-corrects-metabolism-and-restores-function-in-the-diabetic-heart-following-hypoxia-reoxygenation
#5
Latt S Mansor, Maria da Luz Sousa Fialho, Georgina Yea, Will A Coumans, James A West, Matthew Kerr, Carolyn A Carr, Joost J F P Luiken, Jan F C Glatz, Rhys D Evans, Julian L Griffin, Damian J Tyler, Kieran Clarke, Lisa C Heather
Aims: The type 2 diabetic heart oxidizes more fat and less glucose, which can impair metabolic flexibility and function. Increased sarcolemmal fatty acid translocase (FAT/CD36) imports more fatty acid into the diabetic myocardium, feeding increased fatty acid oxidation and elevated lipid deposition. Unlike other metabolic modulators that target mitochondrial fatty acid oxidation, we proposed that pharmacologically inhibiting fatty acid uptake, as the primary step in the pathway, would provide an alternative mechanism to rebalance metabolism and prevent lipid accumulation following hypoxic stress...
April 17, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28418387/mitochondria-are-the-powerhouses-of-immunity
#6
REVIEW
Evanna L Mills, Beth Kelly, Luke A J O'Neill
Recent evidence indicates that mitochondria lie at the heart of immunity. Mitochondrial DNA acts as a danger-associated molecular pattern (DAMP), and the mitochondrial outer membrane is a platform for signaling molecules such as MAVS in RIG-I signaling, and for the NLRP3 inflammasome. Mitochondrial biogenesis, fusion and fission have roles in aspects of immune-cell activation. Most important, Krebs cycle intermediates such as succinate, fumarate and citrate engage in processes related to immunity and inflammation, in both innate and adaptive immune cells...
April 18, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28412654/nigella-sativa-a-traditional-tunisian-herbal-medicine-attenuates-bleomycin-induced-pulmonary-fibrosis-in-a-rat-model
#7
Anouar Abidi, Alexandre Robbe, Nadia Kourda, Saloua Ben Khamsa, Alexandre Legrand
The present study investigated the effects of Nigella sativa oil (NSO) on bleomycin (BLM)-induced lung fibrosis in rats. The rat model of pulmonary fibrosis (PF) was established by intratracheal instillation of BLM, and the effect of 1ml/kg oral NSO treatment once daily observed. The effect of NSO was studied over a period of 50daysusing (1)H RMN analysis on the urine and broncho alveolar lavage fluid (Balf) of the rats. Histopathological (inflammation and fibrosis) and immunohistochemical (TGF-β1 density) changes were evaluated...
April 13, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28393699/approaches-of-the-transcriptomic-analysis-in-astrocytes-potential-pharmacological-targets
#8
George E Barreto, Rosa M Gómez, Rosa Helena Bustos, Diego A Forero, Gjumrakch Aliev, Jerzy Leszek, Valentina Echeverria, Janneth Gonzalez
Astrocytes are important glial cells involved in the ionic regulation of the extracellular fluid in the Central Nervous System (CNS), the formation of the blood brain barrier (BBB) and the support to neurons for the maintaining of the Krebs cycle intermediaries. Even though these cells are known to be important for the brain functioning, several of their functions and their development have not been fully elucidated. In this context, identifying the algorithms used for their analysis plays a pivotal role in the development of new strategies in the study of astrocytes...
April 6, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28388555/targeting-mantle-cell-lymphoma-metabolism-and-survival-through-simultaneous-blockade-of-mtor-and-nuclear-transporter-exportin-1
#9
Kazumasa Sekihara, Kaori Saitoh, Lina Han, Stefan Ciurea, Shinichi Yamamoto, Mika Kikkawa, Saiko Kazuno, Hikari Taka, Naoko Kaga, Hajime Arai, Takashi Miida, Michael Andreeff, Marina Konopleva, Yoko Tabe
Mantle cell lymphoma (MCL) is an aggressive B-cell lymphoma with poor prognosis, characterized by aberrant expression of growth-regulating and oncogenic effectors and requiring novel anticancer strategies. The nuclear transporter exportin-1 (XPO1) is highly expressed in MCL and is associated with its pathogenesis. mTOR signaling, a central regulator of cell metabolism, is frequently activated in MCL and is also an important therapeutic target in this cancer. This study investigated the antitumor effects and molecular/metabolic changes induced by the combination of the small-molecule selective inhibitor XPO1 inhibitor KPT-185 and the dual mTORC1/2 kinase inhibitor AZD-2014 on MCL cells...
March 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/28379214/impact-of-recurrent-hypoglycemic-stress-on-hindbrain-a2-nerve-cell-energy-metabolism-and-catecholamine-biosynthesis-modulation-by-estradiol
#10
Pratistha Tamrakar, Karen P Briski
It is unclear if habituation of hindbrain A2 metabolo‑sensory neurons to recurrent insulin-induced hypoglycemia (RIIH) correlates with estradiol-dependent adjustments in energy metabolism that favor positive energy balance. Laser-microdissected A2 cells from estradiolor oil-implanted ovariectomized female rats were analyzed by Western blot to assess effects of three prior daily insulin injections on basal and hypoglycemic patterns of catecholamine biosynthetic enzyme dopamine-beta-hydroxylase (DβH) and rate-limiting energy pathway enzyme protein expression...
2017: Acta Neurobiologiae Experimentalis
https://www.readbyqxmd.com/read/28371363/diurnal-expression-of-proteins-in-the-retina-of-the-blind-cone-rod-homeobox-crx-mouse-and-the-129-sv-mouse-a-proteomic-study
#11
Morten Møller, Martin Fredensborg Rath, Maja Ludvigsen, Bent Honoré, Henrik Vorum
PURPOSE: The vertebrate retina contains a circadian clock participating in adaptations to day and night vision. This peripheral clock is independent of the master clock in the suprachiasmatic nucleus (SCN). The retinal clock is located in several cell types, including the photoreceptors. To investigate the role of the circadian clock of the photoreceptor cells in regulation of retinal protein rhythms, we analysed diurnal protein expression in the photoreceptor-deficient cone-rod homeobox knockout mouse (Crx(-/-) ) and the 129/Sv mouse...
March 28, 2017: Acta Ophthalmologica
https://www.readbyqxmd.com/read/28363960/genetic-in-stability-of-2-6-dichlorobenzamide-bam-catabolism-in-aminobacter-sp-msh1-biofilms-under-carbon-starved-conditions
#12
Benjamin Horemans, Bart Raes, Hannelore Brocatus, Jeroen T'Syen, Caroline Rombouts, Lynn Vanhaecke, Johan Hofkens, Dirk Springael
Aminobacter sp. MSH1 grows on and mineralizes the groundwater micropollutant 2,6-dichlorobenzamide (BAM) and is of interest for BAM removal in drinking water treatment plants (DWTPs). The BAM-catabolic genes in MSH1 are located on plasmid pBAM1 carrying bbdA encoding the conversion of BAM to 2,6-dichlorobenzoic acid (2,6-DCBA) (BbdA(+) phenotype) and plasmid pBAM2 carrying gene clusters encoding the conversion of 2,6-DCBA to TCA cycle intermediates (Dcba(+) phenotype). Indications exist that MSH1 loses easily its BAM-catabolic phenotype...
March 31, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28355531/using-a-genome-scale-metabolic-network-model-to-elucidate-the-mechanism-of-chloroquine-action-in-plasmodium-falciparum
#13
Shivendra G Tewari, Sean T Prigge, Jaques Reifman, Anders Wallqvist
Chloroquine, long the default first-line treatment against malaria, is now abandoned in large parts of the world because of widespread drug-resistance in Plasmodium falciparum. In spite of its importance as a cost-effective and efficient drug, a coherent understanding of the cellular mechanisms affected by chloroquine and how they influence the fitness and survival of the parasite remains elusive. Here, we used a systems biology approach to integrate genome-scale transcriptomics to map out the effects of chloroquine, identify targeted metabolic pathways, and translate these findings into mechanistic insights...
March 22, 2017: International Journal for Parasitology, Drugs and Drug Resistance
https://www.readbyqxmd.com/read/28350967/molecular-hydrogen-potentiates-beneficial-anti-infarct-effect-of-hypoxic-postconditioning-in-isolated-rat-hearts-novel-cardioprotective-intervention
#14
Marek Zálešák, Branislav Kura, Ján Graban, Veronika Ledvényiová-Farkašová, Jan Slezak, Tatiana Ravingerova
Generation of free radicals through incomplete reduction of oxygen during ischemia/ reperfusion is well-described. On the other hand, molecular hydrogen (H<sub>2</sub>) reduces oxidative stress due to its ability to react with strong oxidants and easily penetrate cells by diffusion, without disturbing metabolic redox reactions. This study was designed to explore cardioprotective potential of hypoxic postconditioning (HpostC) against ischemia/reperfusion (30-min global I/120-min R) in isolated rat hearts using oxygen-free Krebs-Henseleit buffer (KHB)...
March 28, 2017: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28344557/dissecting-target-toxic-tissue-and-tissue-specific-responses-of-irinotecan-in-rats-using-metabolomics-approach
#15
Yiran Yao, Pei Zhang, Jing Wang, Jiaqing Chen, Yong Wang, Yin Huang, Zunjian Zhang, Fengguo Xu
As an anticancer agent, irinotecan (CPT-11) has been widely applied in clinical, especially in the treatment of colorectal cancer. However, its clinical use has long been limited by the side effects and potential tissue toxicity. To discriminate the target toxic tissues and dissect the specific response of target tissues after CPT-11 administration in rats, untargeted metabolomic study was conducted. First, differential metabolites between CPT-11 treated group and control group in each tissue were screened out...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28342810/expression-and-putative-role-of-mitochondrial-transport-proteins-in-cancer
#16
REVIEW
Oleksandr Lytovchenko, Edmund R S Kunji
Cancer cells undergo major changes in energy and biosynthetic metabolism. One of them is the Warburg effect, in which pyruvate is used for fermentation rather for oxidative phosphorylation. Another major one is their increased reliance on glutamine, which helps to replenish the pool of Krebs cycle metabolites used for other purposes, such as amino acid or lipid biosynthesis. Mitochondria are central to these alterations, as the biochemical pathways linking these processes run through these organelles. Two membranes, an outer and inner membrane, surround mitochondria, the latter being impermeable to most organic compounds...
March 22, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28334892/inhibition-of-homologous-phosphorolytic-ribonucleases-by-citrate-may-represent-an-evolutionarily-conserved-communicative-link-between-rna-degradation-and-central-metabolism
#17
Carlanne M Stone, Louise E Butt, Joshua C Bufton, Daniel C Lourenco, Darren M Gowers, Andrew R Pickford, Paul A Cox, Helen A Vincent, Anastasia J Callaghan
Ribonucleases play essential roles in all aspects of RNA metabolism, including the coordination of post-transcriptional gene regulation that allows organisms to respond to internal changes and environmental stimuli. However, as inherently destructive enzymes, their activity must be carefully controlled. Recent research exemplifies the repertoire of regulatory strategies employed by ribonucleases. The activity of the phosphorolytic exoribonuclease, polynucleotide phosphorylase (PNPase), has previously been shown to be modulated by the Krebs cycle metabolite citrate in Escherichia coli...
March 3, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28334508/dietary-fatty-acids-influence-sperm-quality-and-function
#18
A Ferramosca, N Moscatelli, M Di Giacomo, V Zara
Recently, obesity has been linked to male infertility. In animal models the administration of a high-fat diet caused a reduction in sperm quality, by impairing gamete energy metabolism. The aim of this study was to investigate a possible effect of dietary fatty acids supplementation in the modulation of sperm energy metabolism and, in turn, in the improvement of sperm quality in rats fed a high-fat diet. Sexually mature male Sprague-Dawley rats were divided into four groups and fed for 4 weeks a standard diet (control group), a high-fat diet (enriched in 35% of fat and 15% sucrose), a high-fat diet supplemented with 2...
May 2017: Andrology
https://www.readbyqxmd.com/read/28323106/implications-of-epigallocatechin-3-gallate-in-cultured-human-sertoli-cells-glycolytic-and-oxidative-profile
#19
Tânia R Dias, Marco G Alves, Joaquina Silva, Alberto Barros, Mário Sousa, Susana Casal, Branca M Silva, Pedro F Oliveira
Sertoli cells are crucial for the success of spermatogenesis, which is the biological process that ensures male fertility. These cells present high metabolic rates, being often subjected to high oxidative stress levels that, if uncontrolled, may compromise male fertility. Since the most abundant tea catechin, epigallocatechin-3-gallate (EGCG), has demonstrated a potent preventive activity against oxidative stress, we have evaluated its effect at concentrations of 5 and 50μM, on the metabolism, mitochondrial functionality and oxidative profile of human Sertoli cells (hSCs)...
March 18, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
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
#20
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)
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