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NAD+ increase AND Nicotinamide

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https://www.readbyqxmd.com/read/29146412/skeletal-muscle-overexpression-of-nicotinamide-phosphoribosyl-transferase-in-mice-coupled-with-voluntary-exercise-augments-exercise-endurance
#1
Sheila R Costford, Bram Brouwers, Meghan E Hopf, Lauren M Sparks, Mauro Dispagna, Ana P Gomes, Heather H Cornnell, Chris Petucci, Peter Phelan, Hui Xie, Fanchao Yi, Glenn A Walter, Timothy F Osborne, David A Sinclair, Randall L Mynatt, Julio E Ayala, Stephen J Gardell, Steven R Smith
OBJECTIVE: Nicotinamide phosphoribosyl transferase (NAMPT) is the rate-limiting enzyme in the salvage pathway that produces nicotinamide adenine dinucleotide (NAD(+)), an essential co-substrate regulating a myriad of signaling pathways. We produced a mouse that overexpressed NAMPT in skeletal muscle (NamptTg) and hypothesized that NamptTg mice would have increased oxidative capacity, endurance performance, and mitochondrial gene expression, and would be rescued from metabolic abnormalities that developed with high fat diet (HFD) feeding...
November 6, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29144820/pheochromocytoma-a-genetic-and-diagnostic-update
#2
Leilani B Mercado-Asis, Katherine I Wolf, Ivana Jochmanova, David Taïeb
OBJECTIVE: Pheochromocytomas and paragangliomas (PPGLs) are neuroendocrine tumors derived from adrenal or extra-adrenal locations, respectively. Upon suspicion of PPGL, specific metabolomic, molecular, biochemical, imaging, and histopathological studies are performed to prove, localize, treat, and monitor disease progression. Recently, improved diagnostic tools allow physicians to accurately diagnose PPGL, even in patients presenting with small (less than 1 cm) or biochemically silent tumors, which previously delayed proper detection and treatment...
November 16, 2017: Endocrine Practice
https://www.readbyqxmd.com/read/29123192/targeted-mitochondrial-therapy-using-mitoq-shows-equivalent-renoprotection-to-angiotensin-converting-enzyme-inhibition-but-no-combined-synergy-in-diabetes
#3
Micheal S Ward, Nicole B Flemming, Linda A Gallo, Amelia K Fotheringham, Domenica A McCarthy, Aowen Zhuang, Peter H Tang, Danielle J Borg, Hannah Shaw, Benjamin Harvie, David R Briskey, Llion A Roberts, Manuel R Plan, Michael P Murphy, Mark P Hodson, Josephine M Forbes
Mitochondrial dysfunction is a pathological mediator of diabetic kidney disease (DKD). Our objective was to test the mitochondrially targeted agent, MitoQ, alone and in combination with first line therapy for DKD. Intervention therapies (i) vehicle (D); (ii) MitoQ (DMitoQ;0.6 mg/kg/day); (iii) Ramipril (DRam;3 mg/kg/day) or (iv) combination (DCoAd) were administered to male diabetic db/db mice for 12 weeks (n = 11-13/group). Non-diabetic (C) db/m mice were followed concurrently. No therapy altered glycaemic control or body weight...
November 9, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29120608/biochemical-gas-sensors-biosniffers-using-forward-and-reverse-reactions-of-secondary-alcohol-dehydrogenase-for-breath-isopropanol-and-acetone-as-potential-volatile-biomarkers-of-diabetes-mellitus
#4
Po-Jen Chien, Takuma Suzuki, Masato Tsujii, Ming Ye, Isao Minami, Kanako Toda, Hiromi Otsuka, Koji Toma, Takahiro Arakawa, Kouji Araki, Yasuhiko Iwasaki, Kayoko Shinada, Yoshihiro Ogawa, Kohji Mitsubayashi
This study describes two biosniffers to determine breath acetone and isopropanol (IPA) levels and applies them for breath measurement in healthy subjects and diabetic patients. Secondary alcohol dehydrogenase (S-ADH) can reduce acetone and oxidize nicotinamide adenine dinucleotide (NADH to NAD(+)) in a weak acid environment. NADH can be excited by 340 nm excitation lights and subsequently emit 490 nm fluorescence. Therefore, acetone can be measured by the decrease in NADH fluorescence intensity. S-ADH can also oxidize IPA and reduce NAD(+) to NADH when it is in an alkaline environment...
November 9, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29118980/sirt1-dependent-modulation-of-methylation-and-acetylation-of-histone-h3-on-lysine-9-h3k9-in-the-zygotic-pronuclei-improves-porcine-embryo-development
#5
Katerina Adamkova, Young-Joo Yi, Jaroslav Petr, Tereza Zalmanova, Kristyna Hoskova, Pavla Jelinkova, Jiri Moravec, Milena Kralickova, Miriam Sutovsky, Peter Sutovsky, Jan Nevoral
Background: The histone code is an established epigenetic regulator of early embryonic development in mammals. The lysine residue K9 of histone H3 (H3K9) is a prime target of SIRT1, a member of NAD(+)-dependent histone deacetylase family of enzymes targeting both histone and non-histone substrates. At present, little is known about SIRT1-modulation of H3K9 in zygotic pronuclei and its association with the success of preimplantation embryo development. Therefore, we evaluated the effect of SIRT1 activity on H3K9 methylation and acetylation in porcine zygotes and the significance of H3K9 modifications for early embryonic development...
2017: Journal of Animal Science and Biotechnology
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/29108235/regulation-of-sirt3-signal-related-metabolic-reprogramming-in-gastric-cancer-by-helicobacter-pylori-oncoprotein-caga
#7
Do Yeon Lee, Dawoon E Jung, Sung Sook Yu, Yeo Song Lee, Beom Ku Choi, Yong Chan Lee
Injection of the Helicobacter pylori cytotoxin-associated gene A (CagA) is closely associated with the development of chronic gastritis and gastric cancer. Individuals infected with H. pylori possessing the CagA protein produce more reactive oxygen species (ROS) and show an increased risk of developing gastric cancer. Sirtuins (SIRTs) are nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylases and mitochondrial SIRT3 is known to be a tumor suppressor via its ability to suppress ROS and hypoxia inducible factor 1α (HIF-1α)...
October 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/29104634/endogenous-nampt-upregulation-is-associated-with-diabetic-nephropathy-inflammatory-fibrosis-through-the-nf-%C3%AE%C2%BAb-p65-and-sirt1-pathway-nmn-alleviates-diabetic-nephropathy-inflammatory-fibrosis-by-inhibiting-endogenous-nampt
#8
Ye Chen, Yuzhen Liang, Tingting Hu, Riming Wei, Congjie Cai, Ping Wang, Lingyu Wang, Wei Qiao, Leping Feng
Nicotinamide phosphoribosyltransferase (Nampt) is a key enzyme in the nicotinamide adenine dinucleotide (NAD(+)) biosynthetic pathway. Exogenous extra cellular Nampt has been reported to increase the synthesis of pro-fibrotic molecules in various types of renal cells. However, the role of endogenous Namptenzymatic activity in diabetic renal cells, particularly those associated with inflammation and fibrosis through the nuclear factor (NF)-κB p65 and sirtuin 1 (Sirt1) pathway is still unknown. In the present study, a possible mechanism by which endogenous Nampt upregulation affects the expression of pro-inflammatory and pro-fibrotic cytokines in vivo and in vitro, is reported...
November 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/29091865/the-role-of-sirt1-in-diabetic-retinopathy
#9
REVIEW
Hedyieh Karbasforooshan, Gholamreza Karimi
The prevalence of diabetes mellitus (DM), has been increasing worldwide. Diabetic retinopathy (DR) is the most common microvascular complication in diabetes. It is a multifactorial disease that occurs primarily through the long-term detrimental effects of hyperglycemia. The pathogenesis of DR is complex, including inflammation, oxidative stress and advanced glycation end products (AGES). SIRT1 is a nicotinamide adenosine dinucleotide (NAD+)-dependent deacetylase that removes acetyl groups from proteins which can be implicated in DR...
October 26, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29074724/conversion-of-prps-hexamer-to-monomer-by-ampk-mediated-phosphorylation-inhibits-nucleotide-synthesis-in-response-to-energy-stress
#10
Xu Qian, Xinjian Li, Lin Tan, Jong-Ho Lee, Yan Xia, Qingsong Cai, Yanhua Zheng, Hongxia Wang, Philip L Lorenzi, Zhimin Lu
Tumors override energy stress to grow. However, how nucleotide synthesis is regulated under energy stress is unclear. We demonstrate here that glucose deprivation or hypoxia results in the AMPK-mediated phosphorylation of phosphoribosyl pyrophosphate synthetase (PRPS) 1 S180 and PRPS2 S183, leading to conversion of PRPS hexamers to monomers and thereby inhibiting PRPS1/2 activity, nucleotide synthesis, and nicotinamide adenine dinucleotide (NAD) production. Knock-in of non-phosphorylatable PRPS1/2 mutants, which have uninhibited activity, in brain tumor cells under energy stress exhausts cellular ATP and NADPH and increases ROS levels, thereby promoting cell apoptosis...
October 26, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/29069580/nicotinamide-prevents-sweet-beverage-induced-hepatic-steatosis-in-rats-by-regulating-the-g6pd-nadph-nadp-and-gsh-gssg-ratios-and-reducing-oxidative-and-inflammatory-stress
#11
Selene Ángeles Mejía, Luis Arturo Baiza Gutman, Clara Ortega Camarillo, Rafael Medina Navarro, Martha Catalina Sánchez Becerra, Leticia Damasio Santana, Miguel Cruz, Elizabeth Hernández Pérez, Margarita Díaz Flores
The disruption of redox state homeostasis, the overexpression of lipogenic transcription factors and enzymes, and the increase in lipogenic precursors induced by sweetened beverages are determinants of the development of nonalcoholic fatty liver disease. This study evaluated the action of nicotinamide (NAM) on the expression of glucose-6-phosphate dehydrogenase (G6PD) and redox, oxidative, and inflammatory states in a model of nonalcoholic hepatic steatosis induced by high and chronic consumption of carbohydrates...
October 22, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/29054583/dietary-resveratrol-increases-mid-life-fecundity-of-female-nothobranchius-guentheri
#12
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/29046881/nmnat3-is-protective-against-the-effects-of-neonatal-cerebral-hypoxia-ischemia
#13
Rafael Galindo, Marianne Banks Greenberg, Toshiyuki Araki, Yo Sasaki, Nehali Mehta, Jeffrey Milbrandt, David M Holtzman
OBJECTIVE: To determine whether the NAD+ biosynthetic protein, nicotinamide mononucleotide adenylyltransferase-3 (NMNAT3), is a neuroprotective inducible enzyme capable of decreasing cerebral injury after neonatal hypoxia-ischemia (H-I) and reducing glutamate receptor-mediated excitotoxic neurodegeneration of immature neurons. METHODS: Using NMNAT3-overexpressing mice we investigated whether increases in brain NMNAT3 reduced cerebral tissue loss following H-I. We then employed biochemical methods from injured neonatal brains to examine the inducibility of NMNAT3 and the mechanism of NMNAT3-dependent neuroprotection...
October 2017: Annals of Clinical and Translational Neurology
https://www.readbyqxmd.com/read/29039506/hypothermic-machine-perfusion-ameliorates-inflammation-during-ischemia%C3%A2-reperfusion-injury-via-sirtuin%C3%A2-1%C3%A2-mediated-deacetylation-of-nuclear-factor%C3%A2-%C3%AE%C2%BAb-p65-in-rat-livers-donated-after-circulatory-death
#14
Cheng Zeng, Xiaoyan Hu, Weiyang He, Yanfeng Wang, Ling Li, Yan Xiong, Qifa Ye
Hypothermic machine perfusion (HMP) effectively reduces ischemia‑reperfusion injury (IRI) in livers donated after circulatory death (DCD) when compared with cold storage (CS). However, the underlying mechanisms remain unclear. The current study aimed to investigate the cellular mechanisms by which HMP ameliorates the inflammatory response during IRI. Adult male Sprague‑Dawley rat livers were exposed to 30 min of warm ischemia following cardiac arrest and preserved by CS or HMP for 3 h (n=3 per group)...
December 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28974242/oleate-ameliorates-palmitate-induced-reduction-of-nampt-activity-and-nad-levels-in-primary-human-hepatocytes-and-hepatocarcinoma-cells
#15
Melanie Penke, Susanne Schuster, Theresa Gorski, Rolf Gebhardt, Wieland Kiess, Antje Garten
BACKGROUND: Nicotinamide phosphoribosyltransferase (NAMPT) and nicotinamide adenine dinucleotide (NAD) levels are crucial for liver function. The saturated fatty acid palmitate and the unsaturated fatty acid oleate are the main free fatty acids in adipose tissue and human diet. We asked how these fatty acids affect cell survival, NAMPT and NAD levels in HepG2 cells and primary human hepatocytes. METHODS: HepG2 cells were stimulated with palmitate (0.5mM), oleate (1mM) or a combination of both (0...
October 3, 2017: Lipids in Health and Disease
https://www.readbyqxmd.com/read/28923496/deficiency-of-the-mitochondrial-nad-kinase-causes-stress-induced-hepatic-steatosis-in-mice
#16
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 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28916720/glucose-availability-controls-adipogenesis-in-mouse-3t3-l1-adipocytes-via-up-regulation-of-nicotinamide-metabolism
#17
Robert M Jackson, Beth A Griesel, Jami M Gurley, Luke I Szweda, Ann Louise Olson
Expansion of adipose tissue in response to a positive energy balance underlies obesity and occurs through both hypertrophy of existing cells and increased differentiation of adipocyte precursors (hyperplasia). To better understand the nutrient signals that promote adipocyte differentiation, we investigated the role of glucose availability in regulating adipocyte differentiation and maturation. 3T3-L1 preadipocytes were grown and differentiated in medium containing a standard differentiation hormone mixture and either 4 or 25 mm glucose...
November 10, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28915567/melatonin-inhibits-sirt1-dependent-nampt-and-nfat5-signaling-in-chondrocytes-to-attenuate-osteoarthritis
#18
Jia Yi Guo, Feng Li, Yong Bing Wen, Hong Xun Cui, Ma Long Guo, Lin Zhang, Yun Fei Zhang, Yan Jin Guo, Yan Xing Guo
Osteoarthritis (OA) is a degenerative joint disease mainly characterized by cartilage degradation. Interleukin-1β (IL-1β) contributes to OA pathogenesis by enhancing oxidative stress and inflammation. Melatonin reportedly elicits potent protection against OA. However, the role of melatonin and underlying mechanism in IL-1β-stimulated chondrocytes remain largely unclear. In this study, we found that melatonin inhibited IL-1β-induced toxicity and sirtuin 1 (Sirt1) enhancement in human chondrocytes. Melatonin reduced the IL-1β-increased nicotinamide phosphoribosyltransferase (NAMPT) expression and the NAD(+) level in chondrocytes in a Sirt1-dependent manner...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28899971/matrix-screen-identifies-synergistic-combination-of-parp-inhibitors-and-nicotinamide-phosphoribosyltransferase-nampt-inhibitors-in-ewing-sarcoma
#19
Christine M Heske, Mindy I Davis, Joshua T Baumgart, Kelli M Wilson, Michael V Gormally, Lu Chen, Xiaohu Zhang, Michele Ceribelli, Damien Duveau, Rajarshi Guha, Marc Ferrer, Fernanda I Arnaldez, Jiuping Jay Ji, Huong-Lan Tran, Yiping Zhang, Arnulfo Mendoza, Lee J Helman, Craig J Thomas
PURPOSE: While many cancers are showing remarkable responses to targeted therapies, pediatric sarcomas, including Ewing sarcoma, remain recalcitrant. To broaden the therapeutic landscape, we explored the in vitro response of Ewing sarcoma cell lines against a large collection of investigational and approved drugs to identify candidate combinations. EXPERIMENTAL DESIGN: Drugs displaying activity as single agents were evaluated in combinatorial (matrix) format to identify highly active, synergistic drug combinations, and combinations were subsequently validated in multiple cell lines using various agents from each class...
September 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28882480/short-term-administration-of-nicotinamide-mononucleotide-preserves-cardiac-mitochondrial-homeostasis-and-prevents-heart-failure
#20
Rongli Zhang, Yuyan Shen, Lin Zhou, Panjamaporn Sangwung, Hisashi Fujioka, Lilei Zhang, Xudong Liao
Heart failure is associated with mitochondrial dysfunction so that restoring or improving mitochondrial health is of therapeutic importance. Recently, reduction in NAD(+) levels and NAD(+)-mediated deacetylase activity has been recognized as negative regulators of mitochondrial function. Using a cardiac specific KLF4 deficient mouse line that is sensitive to stress, we found mitochondrial protein hyperacetylation coupled with reduced Sirt3 and NAD(+) levels in the heart before stress, suggesting that the KLF4-deficient heart is predisposed to NAD(+)-associated defects...
September 5, 2017: Journal of Molecular and Cellular Cardiology
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