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https://www.readbyqxmd.com/read/28052592/innocent-but-deadly-nontoxic-organoiridium-catalysts-promote-selective-cancer-cell-death
#1
Lu Yang, Sohini Bose, Anh H Ngo, Loi H Do
We demonstrate that nontoxic organoiridum complexes can selectively chemosensitize cancer cells toward platinum antiproliferative agents. Treatment of human cancer cells (breast, colon, eye/retina, head/neck, lung, ovary, and blood) with the iridium chemosensitizers led to lowering of the 50 % growth inhibition concentration (IC50 ) of the Pt drug carboplatin by up to ∼30-50 %. Interestingly, non-cancer cells were mostly resistant to the chemosensitizing effects of the iridium complexes. Cell culture studies indicate that cancer cells that were administered with Ir show significantly higher reactive oxygen species concentrations as well as NAD(+) /NADH ratios (oxidized vs...
January 4, 2017: ChemMedChem
https://www.readbyqxmd.com/read/28035366/inhibitory-effects-of-alpha-lipoic-acid-on-oxidative-stress-in-the-rostral-ventrolateral-medulla-in-rats-with-salt-induced-hypertension
#2
Yu-Peng Huang, Hong-Yan Jin, Hui-Ping Yu
Oxidative stress in the rostral ventrolateral medulla (RVLM) plays an important role in the pathophysiology of hypertension. Alpha‑lipoic acid (ALA) is widely recognized for its potent superoxide inhibitory properties, and it can safely penetrate deep into the brain. The aim of this study was to explore whether ALA supplementation attenuates hypertensive responses and cardiac hypertrophy by decreasing the NAD(P)H oxidase (NOX)-derived overproduction of reactive oxygen species (ROS) in the mitochondria in the RVLM, and thus attenuating the development of salt‑induced hypertension...
February 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28032230/protective-effect-of-p7c3-on-retinal-ganglion-cells-from-optic-nerve-injury
#3
Hidehiro Oku, Seita Morishita, Taeko Horie, Yuko Nishikawa, Teruyo Kida, Masashi Mimura, Shota Kojima, Tsunehiko Ikeda
PURPOSE: To determine whether P7C3-A20, a proneurogenic neuroprotective agent, can protect the retinal ganglion cells (RGCs) of rats from optic nerve crushing. METHODS: The left optic nerve of 67 rats was crushed, and 5.0 mg/kg/day of P7C3-A20 (crush-P7C3) or its vehicle (crush-placebo) was injected intraperitoneally for 3 days from one day prior to the crushing. The protective effects were determined by the number of Tuj-1-stained RGCs and by the ratio of the mRNA levels of BAX/Bcl-2 on day 7...
December 28, 2016: Japanese Journal of Ophthalmology
https://www.readbyqxmd.com/read/28025168/inversion-of-substrate-stereoselectivity-of-horse-liver-alcohol-dehydrogenase-by-substitutions-of-ser-48-and-phe-93
#4
Keehyuk Kim, Bryce V Plapp
The substrate specificities of alcohol dehydrogenases (ADH) are of continuing interest for understanding the physiological functions of these enzymes. Ser-48 and Phe-93 have been identified as important residues in the substrate binding sites of ADHs, but more comprehensive structural and kinetic studies are required. The S48T substitution in horse ADH1E has small effects on kinetic constants and catalytic efficiency (V/Km) with ethanol, but decreases activity with benzyl alcohol and affinity for 2,2,2-trifluoroethanol (TFE) and 2,3,4,5,6-pentafluorobenzyl alcohol (PFB)...
December 23, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28007420/pyruvate-dehydrogenase-complex-regulator-pdhr-gene-deletion-boosts-glucose-metabolism-in-escherichia-coli-under-oxygen-limited-culture-conditions
#5
Soya Maeda, Kumiko Shimizu, Chie Kihira, Yuki Iwabu, Ryuichi Kato, Makoto Sugimoto, Satoru Fukiya, Masaru Wada, Atsushi Yokota
Pyruvate dehydrogenase complex regulator (PdhR) is a transcriptional regulator that negatively regulates formation of pyruvate dehydrogenase complex (PDHc), NADH dehydrogenase (NDH)-2, and cytochrome bo3 oxidase in Escherichia coli. To investigate the effects of a PdhR defect on glucose metabolism, a pdhR deletion mutant was derived from the wild-type E. coli W1485 strain by λ Red-mediated recombination. While no difference in the fermentation profiles was observed between the two strains under oxygen-sufficient conditions, under oxygen-limited conditions, the growth level of the wild-type strain was significantly decreased with retarded glucose consumption accompanied by by-production of substantial amounts of pyruvic acid and acetic acid...
December 19, 2016: Journal of Bioscience and Bioengineering
https://www.readbyqxmd.com/read/28003863/resolving-contributions-of-oxygen-consuming-and-ros-generating-enzymes-at-the-synapse
#6
Engy A Abdel-Rahman, Ali M Mahmoud, Abdullah Aaliya, Yasmine Radwan, Basma Yasseen, Abdelrahman Al-Okda, Ahmed Atwa, Eslam Elhanafy, Moaaz Habashy, Sameh S Ali
Disruption of cellular redox homeostasis is implicated in a wide variety of pathologic conditions and aging. A fundamental factor that dictates such balance is the ratio between mitochondria-mediated complete oxygen reduction into water and incomplete reduction into superoxide radical by mitochondria and NADPH oxidase (NOX) enzymatic activity. Here we determined mitochondrial as well as NOX-dependent rates of oxygen consumption in parallel with H2O2 generation in freshly isolated synaptosomes using high resolution respirometry combined with fluorescence or electrochemical sensory...
2016: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/28003588/effectiveness-of-medium-chain-triglyceride-oil-therapy-in-two-japanese-citrin-deficient-siblings-evaluation-using-oral-glucose-tolerance-tests
#7
Hiroki Otsuka, Hideo Sasai, Elsayed Abdelkreem, Norio Kawamoto, Minako Kawamoto, Toshiya Kamiya, Yasuo Tanimoto, Atsuo Kikuchi, Shigeo Kure, Chikahiko Numakura, Kiyoshi Hayasaka, Toshiyuki Fukao
Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD(+) ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis...
2016: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/27973747/quinolinic-acid-induces-neuritogenesis-in-sh-sy5y-neuroblastoma-cells-independently-of-nmda-receptor-activation
#8
Juan-Manuel Hernandez-Martinez, Caroline M Forrest, L Gail Darlington, Robert A Smith, Trevor W Stone
Glutamate and nicotinamide adenine dinucleotide (NAD+) have been implicated in neuronal development and several types of cancer. The kynurenine pathway of tryptophan metabolism includes quinolinic acid (QA) which is both a selective agonist at N-methyl-D-aspartate (NMDA) receptors and also a precursor for the formation of NAD+. The effect of QA on cell survival and differentiation has therefore been examined on SH-SY5Y human neuroblastoma cells. Retinoic acid (RA, 10 μM) induced differentiation of SH-SY5Y cells into a neuronal phenotype showing neurite growth...
December 14, 2016: European Journal of Neuroscience
https://www.readbyqxmd.com/read/27965531/fatty-acid-biosynthesis-inhibition-increases-reduction-potential-in-neuronal-cells-under-hypoxia
#9
Stephen A Brose, Svetlana A Golovko, Mikhail Y Golovko
Recently, we have reported a novel neuronal specific pathway for adaptation to hypoxia through increased fatty acid (FA) biosynthesis followed by esterification into lipids. However, the biological role of this pathway under hypoxia remains to be elucidated. In the presented study, we have tested our hypothesis that activation of FA synthesis maintains reduction potential and reduces lactoacidosis in neuronal cells under hypoxia. To address this hypothesis, we measured the effect of FA synthesis inhibition on [Formula: see text]/NAD(+) and [Formula: see text]/NADP(+) ratios, and lactic acid levels in neuronal SH-SY5Y cells exposed to normoxic and hypoxic conditions...
2016: Frontiers in Neuroscience
https://www.readbyqxmd.com/read/27919756/molecular-identification-and-functional-delineation-of-a-glutathione-reductase-homolog-from-disk-abalone-haliotis-discus-discus-insights-as-a-potent-player-in-host-antioxidant-defense
#10
H M L P B Herath, P D S U Wickramasinghe, S D N K Bathige, R G P T Jayasooriya, Gi-Young Kim, Myoung Ae Park, Chul Kim, Jehee Lee
Glutathione reductase (GSR) is an enzyme that catalyzes the biochemical conversion of oxidized glutathione (GSSG) into the reduced form (GSH). Since the ratio between the two forms of glutathione (GSH/GSSG) is important for the optimal function of GSH to act as an antioxidant against H2O2, the contribution of GSR as an enzymatic regulatory agent to maintain the proper ratio is essential. Abalones are marine mollusks that frequently encounter environmental factors that can trigger the overproduction of reactive oxygen species (ROS) such as H2O2...
December 3, 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27913299/the-inhibitory-effect-of-beta-lapachone-on-rankl-induced-osteoclastogenesis
#11
Dong Ryun Gu, Joon No Lee, Gi-Su Oh, Hyung Jin Kim, Min Seuk Kim, Seoung Hoon Lee
β-lapachone (β-L) is a substrate of reduced nicotinamide adenine dinucleotide (NADH): quinone oxidoreductase 1 (NQO1). NQO1 reduces quinones to hydroquinones using NADH as an electron donor and consequently increases the intracellular NAD+/NADH ratio. The activation of NQO1 by β-L has beneficial effects on several metabolic syndromes, such as obesity, hypertension, and renal injury. However, the effect of β-L on bone metabolism remains unclear. Here, we show that β-L might be a potent inhibitor of receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclastogenesis...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27896382/the-mechanism-of-improved-intracellular-organic-selenium-and-glutathione-contents-in-selenium-enriched-candida-utilis-by-acid-stress
#12
Gao-Chuan Zhang, Da-Hui Wang, Dong-Hua Wang, Gong-Yuan Wei
Batch culture of Candida utilis CCTCC M 209298 for the preparation of selenium (Se)-enriched yeast was carried out under different pH conditions, and maximal intracellular organic Se and glutathione (GSH) contents were obtained in a moderate acid stress environment (pH 3.5). In order to elucidate the physiological mechanism of improved performance of Se-enriched yeast by acid stress, assays of the key enzymes involved in GSH biosynthesis and determinations of energy supply and regeneration were performed. The results indicated that moderate acid stress increased the activity of γ-glutamylcysteine synthetase and the ratios of NADH/NAD(+) and ATP/ADP, although no significant changes in intracellular pH were observed...
November 28, 2016: Applied Microbiology and Biotechnology
https://www.readbyqxmd.com/read/27892932/reciprocal-regulation-of-carbon-monoxide-metabolism-and-the-circadian-clock
#13
Roman Klemz, Silke Reischl, Thomas Wallach, Nicole Witte, Karsten Jürchott, Sabrina Klemz, Veronika Lang, Stephan Lorenzen, Miriam Knauer, Steffi Heidenreich, Min Xu, Jürgen A Ripperger, Michael Schupp, Ralf Stanewsky, Achim Kramer
Circadian clocks are cell-autonomous oscillators regulating daily rhythms in a wide range of physiological, metabolic and behavioral processes. Feedback of metabolic signals, such as redox state, NAD(+)/NADH and AMP/ADP ratios, or heme, modulate circadian rhythms and thereby optimize energy utilization across the 24-h cycle. We show that rhythmic heme degradation, which generates the signaling molecule carbon monoxide (CO), is required for normal circadian rhythms as well as circadian metabolic outputs. CO suppresses circadian transcription by attenuating CLOCK-BMAL1 binding to target promoters...
November 28, 2016: Nature Structural & Molecular Biology
https://www.readbyqxmd.com/read/27878107/imaging-the-nadh-nad-homeostasis-for-understanding-the-metabolic-response-of-mycobacterium-to-physiologically-relevant-stresses
#14
Shabir A Bhat, Iram K Iqbal, Ashwani Kumar
The NADH:NAD(+) ratio is the primary indicator of the metabolic state of bacteria. NAD(H) homeostasis is critical for Mycobacterium tuberculosis (Mtb) survival and is thus considered an important drug target, but the spatio-temporal measurements of NAD(H) remain a challenge. Genetically encoded fluorescent biosensors of the NADH:NAD(+) ratios were recently described, paving the way for investigations of the metabolic state of pathogens during infection. Here we have adapted the genetically encoded biosensor Peredox for measurement of the metabolic state of Mtb in vitro and during infection of macrophage cells...
2016: Frontiers in Cellular and Infection Microbiology
https://www.readbyqxmd.com/read/27874078/glutamate-dehydrogenase-activator-bch-stimulating-reductive-amination-prevents-high-fat-high-fructose-diet-induced-steatohepatitis-and-hyperglycemia-in-c57bl-6j-mice
#15
Seung Jin Han, Sung-E Choi, Sang-A Yi, Jong Gab Jung, Ik-Rak Jung, Maureen Shin, Seok Kang, Hyunhee Oh, Hae Jin Kim, Dae Jung Kim, Ji Eun Kwon, Cheol Soo Choi, Kwan Woo Lee, Yup Kang
Individuals with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) induced by high calorie western diet are characterized by enhanced lipogenesis and gluconeogenesis in the liver. Stimulation of reductive amination may shift tricarboxylic acid cycle metabolism for lipogenesis and gluconeogenesis toward glutamate synthesis with increase of NAD+/NADH ratio and thus, ameliorate high calorie diet-induced fatty liver and hyperglycemia. Stimulation of reductive amination through glutamate dehydrogenase (GDH) activator 2-aminobicyclo-(2,2,1)-heptane-2-carboxylic acid (BCH) reduced both de novo lipogenesis and gluconeogenesis but increased the activities of sirtuins and AMP-activated kinase in primary hepatocytes...
November 22, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27871066/a-novel-amino-acid-and-metabolomics-signature-in-mice-overexpressing-muscle-uncoupling-protein-3
#16
Céline Aguer, Brian D Piccolo, Oliver Fiehn, Sean H Adams, Mary-Ellen Harper
Uncoupling protein 3 (UCP3) is highly selectively expressed in skeletal muscle and is known to lower mitochondrial reactive oxygen species and promote fatty acid oxidation; however, the global impact of UCP3 activity on skeletal muscle and whole-body metabolism have not been extensively studied. We utilized untargeted metabolomics to identify novel metabolites that distinguish mice overexpressing UCP3 in muscle, both at rest and after exercise regimens that challenged muscle metabolism, to potentially unmask subtle phenotypes...
November 10, 2016: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/27867097/mitochondrial-remodeling-in-the-liver-following-chronic-alcohol-feeding-to-rats
#17
Derick Han, Heather S Johnson, Madhuri P Rao, Gary Martin, Harsh Sancheti, Kai H Silkwood, Carl W Decker, Kim Tho Nguyen, Joseph G Casian, Enrique Cadenas, Neil Kaplowitz
The feeding of alcohol orally (Lieber-DeCarli diet) to rats has been shown to cause declines in mitochondrial respiration (state III), decreased expression of respiratory complexes, and decreased respiratory control ratios (RCR) in liver mitochondria. These declines and other mitochondrial alterations have led to the hypothesis that alcohol feeding causes "mitochondrial dysfunction" in the liver. If oral alcohol feeding leads to mitochondrial dysfunction, one would predict that increasing alcohol delivery by intragastric (IG) alcohol feeding to rats would cause greater declines in mitochondrial bioenergetics in the liver...
January 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27824080/lycium-barbarum-polysaccharide-attenuates-high-fat-diet-induced-hepatic-steatosis-by-up-regulating-sirt1-expression-and-deacetylase-activity
#18
Li Jia, Wang Li, Jianning Li, Yan Li, Hui Song, Yansong Luan, Hui Qi, Lirong Ma, Xiaohong Lu, Yi Yang
In this study, we aimed to investigate the protective effects and underlying mechanism of Lycium barbarum polysaccharide (LBP) on high-fat-induced nonalcoholic fatty liver disease (NAFLD). Recently, sirtuin 1 (SIRT1) has been shown to play an important role in the regulation of hepatocellular lipid metabolism. Here, we demonstrated that LBP up-regulates SIRT1 deacetylase activity and protein expression by enhancing the NAD(+)/NADH ratio. Subsequently, LBP promoted LKB1 deacetylation and AMPK phosphorylation via SIRT1-dependent signalling...
November 8, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27816420/investigation-of-the-nadh-nad-ratio-in-ralstonia-eutropha-using-the-fluorescence-reporter-protein-peredox
#19
Vijay Tejwani, Franz-Josef Schmitt, Svea Wilkening, Ingo Zebger, Marius Horch, Oliver Lenz, Thomas Friedrich
Ralstonia eutropha is a hydrogen-oxidizing ("Knallgas") bacterium that can easily switch between heterotrophic and autotrophic metabolism to thrive in aerobic and anaerobic environments. Its versatile metabolism makes R. eutropha an attractive host for biotechnological applications, including H2-driven production of biodegradable polymers and hydrocarbons. H2 oxidation by R. eutropha takes place in the presence of O2 and is mediated by four hydrogenases, which represent ideal model systems for both biohydrogen production and H2 utilization...
January 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/27815040/the-addition-of-ketone-bodies-alleviates-mitochondrial-dysfunction-by-restoring-complex-i-assembly-in-a-melas-cellular-model
#20
Samuel Frey, Guillaume Geffroy, Valerie Desquiret-Dumas, Naig Gueguen, Celine Bris, Sophie Belal, Patrizia Amati-Bonneau, Arnaud Chevrollier, Magalie Barth, Daniel Henrion, Guy Lenaers, Dominique Bonneau, Pascal Reynier, Vincent Procaccio
Ketogenic Diet used to treat refractory epilepsy for almost a century may represent a treatment option for mitochondrial disorders for which effective treatments are still lacking. Mitochondrial complex I deficiencies are involved in a broad spectrum of inherited diseases including Mitochondrial Encephalomyopathy, Lactic Acidosis and Stroke-like episodes syndrome leading to recurrent cerebral insults resembling strokes and associated with a severe complex I deficiency caused by mitochondrial DNA (mtDNA) mutations...
January 2017: Biochimica et Biophysica Acta
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