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NAD+ increase AND supplements

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https://www.readbyqxmd.com/read/29217642/nicotinamide-riboside-preserves-cardiac-function-in-a-mouse-model-of-dilated-cardiomyopathy
#1
Nicolas Diguet, Samuel A J Trammell, Cynthia Tannous, Robin Deloux, Jérôme Piquereau, Nathalie Mougenot, Anne Gouge, Mélanie Gressette, Boris Manoury, Jocelyne Blanc, Marie Breton, Jean-François Decaux, Gareth Lavery, István Baczkó, Joffrey Zoll, Anne Garnier, Zhenlin Li, Charles Brenner, Mathias Mericskay
Background -Myocardial metabolic impairment is a major feature in chronic heart failure (HF). As the major coenzyme in fuel oxidation and oxidative phosphorylation and a substrate for enzymes signaling energy stress and oxidative stress response, NAD+ is emerging as a metabolic target in a number of diseases including HF. Little is known on mechanisms regulating homeostasis of NAD+ in the failing heart. Methods -To explore possible alterations of NAD+ homeostasis in the failing heart, we quantified expression of NAD+ biosynthetic enzymes in human failing heart and in the heart of a mouse model of dilated cardiomyopathy (DCM) triggered by SRF transcription factor depletion in the heart (SRFHKO) or of cardiac hypertrophy triggered by transverse aorta constriction (TAC)...
December 7, 2017: Circulation
https://www.readbyqxmd.com/read/29211728/an-open-label-non-randomized-study-of-the-pharmacokinetics-of-the-nutritional-supplement-nicotinamide-riboside-nr-and-its-effects-on-blood-nad-levels-in-healthy-volunteers
#2
Sophia E Airhart, Laura M Shireman, Linda J Risler, Gail D Anderson, G A Nagana Gowda, Daniel Raftery, Rong Tian, Danny D Shen, Kevin D O'Brien
OBJECTIVES: The co-primary objectives of this study were to determine the human pharmacokinetics (PK) of oral NR and the effect of NR on whole blood nicotinamide adenine dinucleotide (NAD+) levels. BACKGROUND: Though mitochondrial dysfunction plays a critical role in the development and progression of heart failure, no mitochondria-targeted therapies have been translated into clinical practice. Recent murine studies have reported associations between imbalances in the NADH/NAD+ ratio with mitochondrial dysfunction in multiple tissues, including myocardium...
2017: PloS One
https://www.readbyqxmd.com/read/29184669/repeat-dose-nrpt-nicotinamide-riboside-and-pterostilbene-increases-nad-levels-in-humans-safely-and-sustainably-a-randomized-double-blind-placebo-controlled-study
#3
Ryan W Dellinger, Santiago Roel Santos, Mark Morris, Mal Evans, Dan Alminana, Leonard Guarente, Eric Marcotulli
NRPT is a combination of nicotinamide riboside (NR), a nicotinamide adenine dinucleotide (NAD+) precursor vitamin found in milk, and pterostilbene (PT), a polyphenol found in blueberries. Here, we report this first-in-humans clinical trial designed to assess the safety and efficacy of a repeat dose of NRPT (commercially known as Basis). NRPT was evaluated in a randomized, double-blind, and placebo-controlled study in a population of 120 healthy adults between the ages of 60 and 80 years. The study consisted of three treatment arms: placebo, recommended dose of NRPT (NRPT 1X), and double dose of NRPT (NRPT 2X)...
2017: NPJ Aging and Mechanisms of Disease
https://www.readbyqxmd.com/read/29156373/mitochondria-targeted-ubiquinone-mitoq-enhances-acetaldehyde-clearance-by-reversing-alcohol-induced-posttranslational-modification-of-aldehyde-dehydrogenase-2-a-molecular-mechanism-of-protection-against-alcoholic-liver-disease
#4
Liuyi Hao, Qian Sun, Wei Zhong, Wenliang Zhang, Xinguo Sun, Zhanxiang Zhou
Alcohol metabolism in the liver generates highly toxic acetaldehyde. Breakdown of acetaldehyde by aldehyde dehydrogenase 2 (ALDH2) in the mitochondria consumes NAD(+) and generates reactive oxygen/nitrogen species, which represents a fundamental mechanism in the pathogenesis of alcoholic liver disease (ALD). A mitochondria-targeted lipophilic ubiquinone (MitoQ) has been shown to confer greater protection against oxidative damage in the mitochondria compared to untargeted antioxidants. The present study aimed to investigate if MitoQ could preserve mitochondrial ALDH2 activity and speed up acetaldehyde clearance, thereby protects against ALD...
November 11, 2017: Redox Biology
https://www.readbyqxmd.com/read/29133854/copper-ii-binding-of-nad-p-h-flavin-oxidoreductase-nfor-enhances-its-cr-vi-reducing-ability
#5
Huawen Han, Zhenmin Ling, Tuoyu Zhou, Rong Xu, Yongxing He, Pu Liu, Xiangkai Li
Microbes can reduce hexavalent chromium Cr (VI) to the less toxic and soluble trivalent Cr (III). Copper stimulates microbial reduction of Cr (VI) by the Bacillus, Ochrobactrum, and Gluconobacter species; however, the mechanism remains unclear. In our study, the rate of Cr (VI) reduction by Staphylococcus aureus LZ-01 was increased by 210 % when supplemented with 60 μM Cu (II). A putative NAD(P)H-flavin oxidoreductase gene (nfoR) was upregulated under Cr (VI) stress. NfoR-knockout mutant displayed impaired reduction of Cr (VI) and Cu (II)-enhanced Cr (VI) reduction by nfoR isogenic mutant was attenuated in the presence of Cu (II)...
November 13, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29118320/nicotinamide-mononucleotide-nmn-supplementation-ameliorates-the-impact-of-maternal-obesity-in-mice-comparison-with-exercise
#6
Golam Mezbah Uddin, Neil A Youngson, Bronte M Doyle, David A Sinclair, Margaret J Morris
Maternal overnutrition increases the risk of long-term metabolic dysfunction in offspring. Exercise improves metabolism partly by upregulating mitochondrial biogenesis or function, via increased levels of nicotinamide adenine dinucleotide (NAD(+)). We have shown that the NAD(+) precursor, nicotinamide mononucleotide (NMN) can reverse some of the negative consequences of high fat diet (HFD) consumption. To investigate whether NMN can impact developmentally-set metabolic deficits, we compared treadmill exercise and NMN injection in offspring of obese mothers...
November 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29073231/poly-adp-ribose-polymerases-inhibitors-prevent-early-mitochondrial-fragmentation-and-hepatocyte-cell-death-induced-by-h2o2
#7
Sandra M Martín-Guerrero, José A Muñoz-Gámez, María-Carmen Carrasco, Javier Salmerón, María Martín-Estebané, Miguel A Cuadros, Julio Navascués, David Martín-Oliva
Poly(ADP-ribose)polymerases (PARPs) are a family of NAD+ consuming enzymes that play a crucial role in many cellular processes, most clearly in maintaining genome integrity. Here, we present an extensive analysis of the alteration of mitochondrial morphology and the relationship to PARPs activity after oxidative stress using an in vitro model of human hepatic cells. The following outcomes were observed: reactive oxygen species (ROS) induced by oxidative treatment quickly stimulated PARPs activation, promoted changes in mitochondrial morphology associated with early mitochondrial fragmentation and energy dysfunction and finally triggered apoptotic cell death...
2017: PloS One
https://www.readbyqxmd.com/read/29054583/dietary-resveratrol-increases-mid-life-fecundity-of-female-nothobranchius-guentheri
#8
Youngjoo Lee, Andrew C Drake, Nicholas O Thomas, Lindsey G Ferguson, Patrick E Chappell, Kate Petersen Shay
The decline of female reproductive function is an early phenotype of aging in humans, occurring only midway through the lifespan. Yet the number of women delaying pregnancy continues to rise in industrialized societies due to personal or socioeconomic circumstances, often resulting in subfertility or difficulty conceiving. There are few defined mechanisms associated with this etiology, and equally few effective therapies. To combat this problem, we used a novel emerging model, Nothobranchius guentheri, that recapitulates the age-associated spectrum of changes that adversely affect human fertility...
October 17, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/29021282/methionine-metabolism-is-essential-for-sirt1-regulated-mouse-embryonic-stem-cell-maintenance-and-embryonic-development
#9
Shuang Tang, Yi Fang, Gang Huang, Xiaojiang Xu, Elizabeth Padilla-Banks, Wei Fan, Qing Xu, Sydney M Sanderson, Julie F Foley, Scotty Dowdy, Michael W McBurney, David C Fargo, Carmen J Williams, Jason W Locasale, Ziqiang Guan, Xiaoling Li
Methionine metabolism is critical for epigenetic maintenance, redox homeostasis, and animal development. However, the regulation of methionine metabolism remains unclear. Here, we provide evidence that SIRT1, the most conserved mammalian NAD(+)-dependent protein deacetylase, is critically involved in modulating methionine metabolism, thereby impacting maintenance of mouse embryonic stem cells (mESCs) and subsequent embryogenesis. We demonstrate that SIRT1-deficient mESCs are hypersensitive to methionine restriction/depletion-induced differentiation and apoptosis, primarily due to a reduced conversion of methionine to S-adenosylmethionine...
November 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28970254/silybin-inhibits-nlrp3-inflammasome-assembly-through-the-nad-sirt2-pathway-in-mice-with-nonalcoholic-fatty-liver-disease
#10
Bangling Zhang, Dan Xu, Linlin She, Zixia Wang, Na Yang, Runbin Sun, Yirui Zhang, Caixia Yan, Qingli Wei, Jiye Aa, Baolin Liu, Guangji Wang, Yuan Xie
Silybin is one of the effective, traditional Chinese medicines used as a hepatoprotective agent in nonalcoholic fatty liver disease (NAFLD) therapy worldwide, and the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome has been recognized as an important factor involved in NAFLD development. However, little is known about the mechanisms of silybin in the regulation of high-fat diet (HFD)-induced liver inflammation. In our study, we found that silybin inhibited endoplasmic reticulum stress and NLRP3 inflammasome activation in the livers of HFD-fed mice and in cultured hepatocytes...
September 27, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28923496/deficiency-of-the-mitochondrial-nad-kinase-causes-stress-induced-hepatic-steatosis-in-mice
#11
Kezhong Zhang, Hyunbae Kim, Zhiyao Fu, Yining Qiu, Zhao Yang, Jiemei Wang, Deqiang Zhang, Xin Tong, Lei Yin, Jing Li, Jianmei Wu, Nathan R Qi, Sander M Houten, Ren Zhang
BACKGROUND & AIMS: The mitochondrial nicotinamide adenine dinucleotide (NAD) kinase (NADK2, also called MNADK) catalyzes phosphorylation of NAD to yield NADP. Little is known about the functions of mitochondrial NADP and MNADK in liver physiology and pathology. We investigated the effects of reduced mitochondrial NADP by deleting MNADK in mice. METHODS: We generated MNADK knockout (KO) mice on a C57BL/6NTac background; mice with a wild-type Mnadk gene were used as controls...
September 18, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28916476/pharmacologic-ascorbate-induces-neuroblastoma-cell-death-by-hydrogen-peroxide-mediated-dna-damage-and-reduction-in-cancer-cell-glycolysis
#12
Enlong Ma, Ping Chen, Heather M Wilkins, Tao Wang, Russell H Swerdlow, Qi Chen
An ascorbate-mediated production of oxidative stress has been shown to retard tumor growth. Subsequent glycolysis inhibition has been suggested. Here, we further define the mechanisms relevant to this observation. Ascorbate was cytotoxic to human neuroblastoma cells through the production of H2O2, which led to ATP depletion, inhibited GAPDH, and non-apoptotic and non-autophagic cell death. The mechanism of cytotoxicity is different when PARP-dependent DNA repair machinery is active or inhibited. Ascorbate-generated H2O2 damaged DNA, activated PARP, depleted NAD+, and reduced glycolysis flux...
September 12, 2017: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/28780322/reduction-of-oxidative-damages-induced-by-titanium-dioxide-nanoparticles-correlates-with-induction-of-the-nrf2-pathway-by-gspe-supplementation-in-mice
#13
Linpeng Niu, Mengjiao Shao, Yuan Liu, Jinfeng Hu, Ruofan Li, Heran Xie, Lixiao Zhou, Lei Shi, Rong Zhang, Yujie Niu
Titanium dioxide nanoparticles (TiO2 NPs) are widely used to additives in cosmetics, pharmaceuticals, paints and foods. Recent studies have demonstrated that TiO2 NPs increased the risk of cancer and the mechanism might relate with oxidative stress. Grape seed procyanidin extract (GSPE) is a natural compound which has been demonstrated to possess a wide array of pharmacological and biochemical actions, including anti-inflammatory, anti-carcinogenic, and antioxidant properties. Our data show that GSPE prevents the changes of histopathology and biomarkers in heart, liver and kidney that occur in mice exposed to TiO2 NPs...
September 25, 2017: Chemico-biological Interactions
https://www.readbyqxmd.com/read/28724806/nicotinamide-mononucleotide-requires-sirt3-to-improve-cardiac-function-and-bioenergetics-in-a-friedreich-s-ataxia-cardiomyopathy-model
#14
Angelical S Martin, Dennis M Abraham, Kathleen A Hershberger, Dhaval P Bhatt, Lan Mao, Huaxia Cui, Juan Liu, Xiaojing Liu, Michael J Muehlbauer, Paul A Grimsrud, Jason W Locasale, R Mark Payne, Matthew D Hirschey
Increasing NAD+ levels by supplementing with the precursor nicotinamide mononucleotide (NMN) improves cardiac function in multiple mouse models of disease. While NMN influences several aspects of mitochondrial metabolism, the molecular mechanisms by which increased NAD+ enhances cardiac function are poorly understood. A putative mechanism of NAD+ therapeutic action exists via activation of the mitochondrial NAD+-dependent protein deacetylase sirtuin 3 (SIRT3). We assessed the therapeutic efficacy of NMN and the role of SIRT3 in the Friedreich's ataxia cardiomyopathy mouse model (FXN-KO)...
July 20, 2017: JCI Insight
https://www.readbyqxmd.com/read/28645327/impact-of-growth-matrix-on-pharmacodynamics-of-antimicrobial-drugs-for-pig-pneumonia-pathogens
#15
Lucy Dorey, Peter Lees
BACKGROUND: The most widely used measure of potency of antimicrobial drugs is Minimum Inhibitory Concentration (MIC). MIC is usually determined under standardised conditions in broths formulated to optimise bacterial growth on a species-by-species basis. This ensures comparability of data between laboratories. However, differences in values of MIC may arise between broths of differing chemical composition and for some drug classes major differences occur between broths and biological fluids such as serum and inflammatory exudate...
June 23, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28642875/rapid-elimination-of-blood-alcohol-using-erythrocytes-mathematical-modeling-and-in-vitro-study
#16
Yuliya G Alexandrovich, Elena A Kosenko, Elena I Sinauridze, Sergey I Obydennyi, Igor I Kireev, Fazoil I Ataullakhanov, Yuriy G Kaminsky
Erythrocytes (RBCs) loaded with alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALD) can metabolize plasma ethanol and acetaldehyde but with low efficiency. We investigated the rate-limiting factors in ethanol oxidation by these enzymes loaded into RBCs. Mathematical modeling and in vitro experiments on human RBCs loaded simultaneously with ADH and ALD (by hypoosmotic dialysis) were performed. The simulation showed that the rate of nicotinamide-adenine dinucleotide (NAD(+)) generation in RBC glycolysis, but not the activities of the loaded enzymes, is the rate-limiting step in external ethanol oxidation...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28603221/modification-of-mitochondrial-function-cytoplasmic-lipid-content-and-cryosensitivity-of-bovine-embryos-by-resveratrol
#17
Takahito Abe, Ryouka Kawahara-Miki, Tomotaka Hara, Tatsuo Noguchi, Takeshi Hayashi, Koumei Shirasuna, Takehito Kuwayama, Hisataka Iwata
Resveratrol is a potent activator of NAD-dependent deacetyltransferase sirtuin-1 (SIRT1) and affects lipid metabolism and ATP generation in somatic cells. In the present study, the effects of supplementing culture medium with resveratrol on lipid metabolism, ATP generation, and cryosensitivity of bovine in vitro produced embryos were investigated. Bovine early cleaved-stage embryos were cultured in medium containing 0 or 0.5 µM resveratrol for 1 or 5 days. Resveratrol treatment for both 1 day and 5 days increased the expression levels of SIRT1 and phosphorylated AMP-activated protein kinase (pAMPK) in the embryos...
October 18, 2017: Journal of Reproduction and Development
https://www.readbyqxmd.com/read/28600316/an-in-vitro-enzyme-system-for-the-production-of-myo-inositol-from-starch
#18
Tomoko Fujisawa, Shohei Fujinaga, Haruyuki Atomi
We developed an in vitro enzyme system to produce myo-inositol from starch. Four enzymes were used, maltodextrin phosphorylase (MalP), phosphoglucomutase (PGM), myo-inositol-3-phosphate synthase (MIPS), and inositol monophosphatase (IMPase). The enzymes were thermostable: MalP and PGM from the hyperthermophilic archaeon Thermococcus kodakarensis, MIPS from the hyperthermophilic archaeon Archaeoglobus fulgidus, and IMPase from the hyperthermophilic bacterium Thermotoga maritima The enzymes were individually produced in Escherichia coli and partially purified by subjecting cell extracts to heat treatment and removing denatured proteins...
August 15, 2017: Applied and Environmental Microbiology
https://www.readbyqxmd.com/read/28584577/antioxidant-mechanism-of-black-garlic-extract-involving-nuclear-factor-erythroid-2-like-factor-2-pathway
#19
Ae Wha Ha, Woo Kyoung Kim
BACKGROUN/OBJECTIVES: Although studies have revealed that black garlic is a potent antioxidant, its antioxidant mechanism remains unclear. The objective of this study was to determine black garlic's antioxidant activities and possible antioxidant mechanisms related to nuclear factor erythroid 2-like factor 2 (Nrf2)-Keap1 complex. METHODS/MATERIALS: After four weeks of feeding rats with a normal fat diet (NF), a high-fat diet (HF), a high-fat diet with 0.5% black garlic extract (HF+BGE 0...
June 2017: Nutrition Research and Practice
https://www.readbyqxmd.com/read/28578808/real-time-monitoring-of-intracellular-redox-changes-in-methylococcus-capsulatus-bath-for-efficient-bioconversion-of-methane-to-methanol
#20
Masahito Ishikawa, Yuya Tanaka, Risa Suzuki, Kota Kimura, Kenya Tanaka, Kazuhide Kamiya, Hidehiro Ito, Souichiro Kato, Toshiaki Kamachi, Katsutoshi Hori, Shuji Nakanishi
This study aimed to develop a novel method for real-time monitoring of the intracellular redox states in a methanotroph Methylococcus capsulatus, using Peredox as a genetically encoded fluorescent sensor of the NADH:NAD(+) ratio. As expected, the fluorescence derived from the Peredox-expressing M. capsulatus transformant increased by supplementation of electron donor compounds (methane and formate), while it decreased by specifically inhibiting the methanol oxidation reaction. Electrochemical measurements confirmed that the Peredox fluorescence reliably represents the intracellular redox changes...
October 2017: Bioresource Technology
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