ECB-ART-42332
Redox Rep
2012 Jan 01;171:28-46. doi: 10.1179/1351000212Y.0000000001.
Show Gene links
Show Anatomy links
NAD+ metabolism and oxidative stress: the golden nucleotide on a crown of thorns.
Massudi H
,
Grant R
,
Guillemin GJ
,
Braidy N
.
Abstract
In the twentieth century, NAD+ research generated multiple discoveries. Identification of the important role of NAD+ as a cofactor in cellular respiration and energy production was followed by discoveries of numerous NAD+ biosynthesis pathways. In recent years, NAD+ has been shown to play a unique role in DNA repair and protein deacetylation. As discussed in this review, there are close interactions between oxidative stress and immune activation, energy metabolism, and cell viability in neurodegenerative disorders and ageing. Profound interactions with regard to oxidative stress and NAD+ have been highlighted in the present work. This review emphasizes the pivotal role of NAD+ in the regulation of DNA repair, stress resistance, and cell death, suggesting that NAD+ synthesis through the kynurenine pathway and/or salvage pathway is an attractive target for therapeutic intervention in age-associated degenerative disorders. NAD+ precursors have been shown to slow down ageing and extend lifespan in yeasts, and protect severed axons from degeneration in animal models neurodegenerative diseases.
PubMed ID: 22340513
PMC ID: PMC6837626
Article link: Redox Rep
Genes referenced: LOC115919910
References [+] :
Adle-Biassette,
DNA breaks detected by in situ end-labelling in dorsal root ganglia of patients with AIDS.
1998, Pubmed
Adle-Biassette, DNA breaks detected by in situ end-labelling in dorsal root ganglia of patients with AIDS. 1998, Pubmed
Ahn, A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. 2008, Pubmed
Aksoy, Regulation of intracellular levels of NAD: a novel role for CD38. 2006, Pubmed
Alano, Poly(ADP-ribose) polymerase-1-mediated cell death in astrocytes requires NAD+ depletion and mitochondrial permeability transition. 2004, Pubmed
Alexander, Indoleamine 2,3-dioxygenase expression in transplanted NOD Islets prolongs graft survival after adoptive transfer of diabetogenic splenocytes. 2002, Pubmed
Anastasiou, SIRT1: linking adaptive cellular responses to aging-associated changes in organismal physiology. 2006, Pubmed
Anderson, Nicotinamide and PNC1 govern lifespan extension by calorie restriction in Saccharomyces cerevisiae. 2003, Pubmed
Anderson, Manipulation of a nuclear NAD+ salvage pathway delays aging without altering steady-state NAD+ levels. 2002, Pubmed
Araki, Increased nuclear NAD biosynthesis and SIRT1 activation prevent axonal degeneration. 2004, Pubmed
BOKMAN, 3-Hydroxyanthranilic acid metabolism. IV. Spectrophotometric evidence for the formation of an intermediate. 1951, Pubmed
Barnham, Neurodegenerative diseases and oxidative stress. 2004, Pubmed
Beal, Kynurenic acid concentrations are reduced in Huntington's disease cerebral cortex. 1992, Pubmed
Beal, Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. 1991, Pubmed
Beckman, The free radical theory of aging matures. 1998, Pubmed
Bedalov, Neuroscience. NAD to the rescue. 2004, Pubmed
Belenky, Nicotinamide riboside promotes Sir2 silencing and extends lifespan via Nrk and Urh1/Pnp1/Meu1 pathways to NAD+. 2007, Pubmed
Belenky, NAD+ metabolism in health and disease. 2007, Pubmed
Bellizzi, A novel VNTR enhancer within the SIRT3 gene, a human homologue of SIR2, is associated with survival at oldest ages. 2005, Pubmed
Beneke, Poly(ADP-ribosyl)ation inhibitors: promising drug candidates for a wide variety of pathophysiologic conditions. 2004, Pubmed
Berger, Metabolic consequences of DNA damage: DNA damage induces alterations in glucose metabolism by activation of poly (ADP-ribose) polymerase. 1986, Pubmed
Berger, Regulation of poly(ADP-ribose) polymerase 1 activity by the phosphorylation state of the nuclear NAD biosynthetic enzyme NMN adenylyl transferase 1. 2007, Pubmed
Berger, The new life of a centenarian: signalling functions of NAD(P). 2004, Pubmed
Bergeron, Modulation of N-methyl-D-aspartate receptor function by glycine transport. 1998, Pubmed
Bieganowski, Discoveries of nicotinamide riboside as a nutrient and conserved NRK genes establish a Preiss-Handler independent route to NAD+ in fungi and humans. 2004, Pubmed
Blander, The Sir2 family of protein deacetylases. 2004, Pubmed
Boasso, HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells. 2007, Pubmed
Boegman, Quinolinic acid neurotoxicity in the nucleus basalis antagonized by kynurenic acid. 1985, Pubmed
Bordone, Calorie restriction, SIRT1 and metabolism: understanding longevity. 2005, Pubmed
Bordone, SIRT1 transgenic mice show phenotypes resembling calorie restriction. 2007, Pubmed
Bordone, Sirt1 regulates insulin secretion by repressing UCP2 in pancreatic beta cells. 2006, Pubmed
Borra, Mechanism of human SIRT1 activation by resveratrol. 2005, Pubmed
Bouchard, PARP-1, a determinant of cell survival in response to DNA damage. 2003, Pubmed
Braidy, Promotion of cellular NAD(+) anabolism: therapeutic potential for oxidative stress in ageing and Alzheimer's disease. 2008, Pubmed
Braidy, Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. 2011, Pubmed
Braidy, Neuroprotective effects of naturally occurring polyphenols on quinolinic acid-induced excitotoxicity in human neurons. 2010, Pubmed
Brown, Implications of interferon-induced tryptophan catabolism in cancer, auto-immune diseases and AIDS. 1991, Pubmed
Bröer, Neutral amino acid transport in epithelial cells and its malfunction in Hartnup disorder. 2005, Pubmed
Buffenstein, The oxidative stress theory of aging: embattled or invincible? Insights from non-traditional model organisms. 2008, Pubmed
Bürkle, Poly(ADP-ribosyl)ation and aging. 2004, Pubmed
Bürkle, Poly(ADP-ribose). The most elaborate metabolite of NAD+. 2005, Pubmed
CHAMBON, Nicotinamide mononucleotide activation of new DNA-dependent polyadenylic acid synthesizing nuclear enzyme. 1963, Pubmed
Cantó, AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. 2009, Pubmed
Cao, Quinolinate phosphoribosyltransferase: kinetic mechanism for a type II PRTase. 2002, Pubmed
Chess, Elevations of endogenous kynurenic acid produce spatial working memory deficits. 2007, Pubmed
Chiarugi, Kynurenine 3-mono-oxygenase activity and neurotoxic kynurenine metabolites increase in the spinal cord of rats with experimental allergic encephalomyelitis. 2001, Pubmed
Chikenji, Protein-diet-induced elevation of 5-phosphoribosyl 1-diphosphate concentrations in mouse liver associated with increased syntheses of various nucleotides and the possible involvement of glucagon. 1984, Pubmed
Clark, Prolonged survival of a murine model of cerebral malaria by kynurenine pathway inhibition. 2005, Pubmed
Coggan, Age and circadian influences on picolinic acid concentrations in human cerebrospinal fluid. 2009, Pubmed
Comaish, Topically applied niacinamide in isoniazid-induced pellagra. 1976, Pubmed
Connick, Quinolinic acid effects on amino acid release from the rat cerebral cortex in vitro and in vivo. 1988, Pubmed
Cosi, Poly(ADP-ribose) polymerase inhibitors protect against MPTP-induced depletions of striatal dopamine and cortical noradrenaline in C57B1/6 mice. 1996, Pubmed
Dali-Youcef, Sirtuins: the 'magnificent seven', function, metabolism and longevity. 2007, Pubmed
Dasgupta, Resveratrol stimulates AMP kinase activity in neurons. 2007, Pubmed
Davies, Protein damage and degradation by oxygen radicals. I. general aspects. 1987, Pubmed
Denu, Vitamins and aging: pathways to NAD+ synthesis. 2007, Pubmed
Di Lisa, Pathophysiological relevance of mitochondria in NAD(+) metabolism. 2001, Pubmed
Dröge, Free radicals in the physiological control of cell function. 2002, Pubmed
ELVEHJEM, Pellagra, a deficiency disease. 1949, Pubmed
Feige, Transcriptional targets of sirtuins in the coordination of mammalian physiology. 2008, Pubmed
Ford, Mammalian Sir2 homolog SIRT7 is an activator of RNA polymerase I transcription. 2006, Pubmed
Frumento, Targeting tumor-related immunosuppression for cancer immunotherapy. 2006, Pubmed
Fujigaki, Lipopolysaccharide induction of indoleamine 2,3-dioxygenase is mediated dominantly by an IFN-gamma-independent mechanism. 2001, Pubmed
Fulco, Glucose restriction inhibits skeletal myoblast differentiation by activating SIRT1 through AMPK-mediated regulation of Nampt. 2008, Pubmed
Furukawa, H2O2 accelerates cellular senescence by accumulation of acetylated p53 via decrease in the function of SIRT1 by NAD+ depletion. 2007, Pubmed
Gaikwad, In vivo role of NAD(P)H:quinone oxidoreductase 1 (NQO1) in the regulation of intracellular redox state and accumulation of abdominal adipose tissue. 2001, Pubmed
Gholson, The pyridine nucleotide cycle. 1966, Pubmed
Gille, Nicotinic acid: pharmacological effects and mechanisms of action. 2008, Pubmed
Grant, Inhibition of indoleamine 2,3-dioxygenase activity in IFN-gamma stimulated astroglioma cells decreases intracellular NAD levels. 2003, Pubmed
Grant, Evidence for increased de novo synthesis of NAD in immune-activated RAW264.7 macrophages: a self-protective mechanism? 1999, Pubmed
Grant, Induction of indolamine 2,3-dioxygenase in primary human macrophages by human immunodeficiency virus type 1 is strain dependent. 2000, Pubmed
Grant, Murine glial cells regenerate NAD, after peroxide-induced depletion, using either nicotinic acid, nicotinamide, or quinolinic acid as substrates. 1998, Pubmed
Grant, IDO induction in IFN-gamma activated astroglia: a role in improving cell viability during oxidative stress. 2000, Pubmed
Grifantini, Tiazofurine ICN Pharmaceuticals. 2000, Pubmed
Gross, Kinetic mechanism of nicotinic acid phosphoribosyltransferase: implications for energy coupling. 1998, Pubmed
Grube, Poly(ADP-ribose) polymerase activity in mononuclear leukocytes of 13 mammalian species correlates with species-specific life span. 1992, Pubmed
Grummt, Epigenetic silencing of RNA polymerase I transcription. 2003, Pubmed
Grune, Degradation of oxidized proteins in mammalian cells. 1997, Pubmed
Guidetti, 3-Hydroxykynurenine and quinolinate: pathogenic synergism in early grade Huntington's disease? 2003, Pubmed
Guillemin, Indoleamine 2,3 dioxygenase and quinolinic acid immunoreactivity in Alzheimer's disease hippocampus. 2005, Pubmed
Guillemin, Implications of the kynurenine pathway and quinolinic acid in Alzheimer's disease. 2002, Pubmed
Guillemin, Implications for the kynurenine pathway and quinolinic acid in amyotrophic lateral sclerosis. 2005, Pubmed
Guillemin, Involvement of quinolinic acid in AIDS dementia complex. 2005, Pubmed
HARMAN, Aging: a theory based on free radical and radiation chemistry. 1956, Pubmed
Haigis, SIRT4 inhibits glutamate dehydrogenase and opposes the effects of calorie restriction in pancreatic beta cells. 2006, Pubmed
Halliwell, Role of free radicals in the neurodegenerative diseases: therapeutic implications for antioxidant treatment. 2001, Pubmed
Halliwell, Oxygen radicals as key mediators in neurological disease: fact or fiction? 1992, Pubmed
Hansen, Increased expression of indoleamine 2,3-dioxygenase in murine malaria infection is predominantly localised to the vascular endothelium. 2004, Pubmed
Hassa, Nuclear ADP-ribosylation reactions in mammalian cells: where are we today and where are we going? 2006, Pubmed
Hayashi, Inhibition of experimental asthma by indoleamine 2,3-dioxygenase. 2004, Pubmed
Hiratsuka, Proteomics-based identification of differentially expressed genes in human gliomas: down-regulation of SIRT2 gene. 2003, Pubmed
Houtkooper, The secret life of NAD+: an old metabolite controlling new metabolic signaling pathways. 2010, Pubmed
Huang, Constitutive histone H2AX phosphorylation on Ser-139 in cells untreated by genotoxic agents is cell-cycle phase specific and attenuated by scavenging reactive oxygen species. 2006, Pubmed
Iida, Accumulation of 8-oxo-2'-deoxyguanosine and increased expression of hMTH1 protein in brain tumors. 2001, Pubmed
Inoue, SIRT2, a tubulin deacetylase, acts to block the entry to chromosome condensation in response to mitotic stress. 2007, Pubmed
Iqbal, TNF regulates cellular NAD+ metabolism in primary macrophages. 2006, Pubmed
Jing, SIRT2 regulates adipocyte differentiation through FoxO1 acetylation/deacetylation. 2007, Pubmed
KORNBERG, The participation of inorganic pyrophosphate in the reversible enzymatic synthesis of diphosphopyridine nucleotide. 1948, Pubmed
Kauppinen, Poly(ADP-ribose) polymerase-1 activation in a primate model of multiple sclerosis. 2005, Pubmed
Khan, Nicotinamide adenine dinucleotide metabolism as an attractive target for drug discovery. 2007, Pubmed
Khan, Molecular basis for the inhibition of human NMPRTase, a novel target for anticancer agents. 2006, Pubmed
Kim, SIRT1 deacetylase protects against neurodegeneration in models for Alzheimer's disease and amyotrophic lateral sclerosis. 2007, Pubmed
Klaidman, Nicotinamide offers multiple protective mechanisms in stroke as a precursor for NAD+, as a PARP inhibitor and by partial restoration of mitochondrial function. 2003, Pubmed
Kletzien, Glucose-6-phosphate dehydrogenase: a "housekeeping" enzyme subject to tissue-specific regulation by hormones, nutrients, and oxidant stress. 1994, Pubmed
Koc, Methionine sulfoxide reductase regulation of yeast lifespan reveals reactive oxygen species-dependent and -independent components of aging. 2004, Pubmed
Kohen, Oxidation of biological systems: oxidative stress phenomena, antioxidants, redox reactions, and methods for their quantification. 2002, Pubmed
Koren, Associations between criteria air pollutants and asthma. 1995, Pubmed
La Piana, Mitochondrial membrane potential supported by exogenous cytochrome c oxidation mimics the early stages of apoptosis. 1998, Pubmed
Lagouge, Resveratrol improves mitochondrial function and protects against metabolic disease by activating SIRT1 and PGC-1alpha. 2006, Pubmed
Li, Sirtuin 2, a mammalian homolog of yeast silent information regulator-2 longevity regulator, is an oligodendroglial protein that decelerates cell differentiation through deacetylating alpha-tubulin. 2007, Pubmed
Lin, Nicotinamide adenine dinucleotide, a metabolic regulator of transcription, longevity and disease. 2003, Pubmed
Lin, Mitochondrial dysfunction and oxidative stress in neurodegenerative diseases. 2006, Pubmed
Liszt, Mouse Sir2 homolog SIRT6 is a nuclear ADP-ribosyltransferase. 2005, Pubmed
Love, Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease. 1999, Pubmed
MASON, The kynurenine transaminase of rat kidney. 1954, Pubmed
MAY, Studies with carboxyl-labeled 3-hydroxyanthranilic and picolinic acids in vivo and in vitro. 1956, Pubmed
MacDonald, Mouse lacking NAD+-linked glycerol phosphate dehydrogenase has normal pancreatic beta cell function but abnormal metabolite pattern in skeletal muscle. 2000, Pubmed
Mackay, Tryptophan metabolism and oxidative stress in patients with chronic brain injury. 2006, Pubmed
Magni, Enzymology of NAD+ synthesis. 1999, Pubmed
Magni, Structure and function of nicotinamide mononucleotide adenylyltransferase. 2004, Pubmed
Magni, Enzymology of mammalian NAD metabolism in health and disease. 2008, Pubmed
Magni, Enzymology of NAD+ homeostasis in man. 2004, Pubmed
Marzulli, Modulation of cytochrome c-mediated extramitochondrial NADH oxidation by contact site density. 1999, Pubmed
Matés, Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. 2000, Pubmed
McCormack, The role of Ca2+ in the regulation of intramitochondrial energy production in heart. 1987, Pubmed
Meral, Lipid peroxidation and antioxidant status in beta-thalassemia. 2000, Pubmed
Michishita, Evolutionarily conserved and nonconserved cellular localizations and functions of human SIRT proteins. 2005, Pubmed
Milne, The Sirtuin family: therapeutic targets to treat diseases of aging. 2008, Pubmed
Moffett, Tryptophan and the immune response. 2003, Pubmed
Mongan, Pyruvate improves redox status and decreases indicators of hepatic apoptosis during hemorrhagic shock in swine. 2002, Pubmed
Monteiro, Niacin metabolite excretion in alcoholic pellagra and AIDS patients with and without diarrhea. 2004, Pubmed
Morita, 3-Hydroxyanthranilic acid, an L-tryptophan metabolite, induces apoptosis in monocyte-derived cells stimulated by interferon-gamma. 2001, Pubmed
Mostoslavsky, Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. 2006, Pubmed
Munn, IDO and tolerance to tumors. 2004, Pubmed
Munn, Prevention of allogeneic fetal rejection by tryptophan catabolism. 1998, Pubmed
Murphy, How mitochondria produce reactive oxygen species. 2009, Pubmed
Naito, Role of oxygen radical and lipid peroxidation in indomethacin-induced gastric mucosal injury. 1998, Pubmed
Nakagawa, SIRT5 Deacetylates carbamoyl phosphate synthetase 1 and regulates the urea cycle. 2009, Pubmed
Obata, Release of dopamine by perfusion with 1-methyl-4-phenylpyridinium ion (MPP(+)) into the striatum is associated with hydroxyl free radical generation. 2001, Pubmed
Osiewacz, Aging in fungi: role of mitochondria in Podospora anserina. 2002, Pubmed
Pearson, Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. 2008, Pubmed
Penberthy, The importance of NAD in multiple sclerosis. 2009, Pubmed
Penberthy, Pharmacological targeting of IDO-mediated tolerance for treating autoimmune disease. 2007, Pubmed
Pentland, Active oxygen mechanisms of UV inflammation. 1994, Pubmed
Pillai, Poly(ADP-ribose) polymerase-1-dependent cardiac myocyte cell death during heart failure is mediated by NAD+ depletion and reduced Sir2alpha deacetylase activity. 2005, Pubmed
Porcu, The emerging therapeutic potential of sirtuin-interacting drugs: from cell death to lifespan extension. 2005, Pubmed
Raff, Axonal self-destruction and neurodegeneration. 2002, Pubmed
Raffaelli, Identification of a novel human nicotinamide mononucleotide adenylyltransferase. 2002, Pubmed
Ramasamy, Metabolic effects of aldose reductase inhibition during low-flow ischemia and reperfusion. 1998, Pubmed
Ray, Evaluation of UV-induced superoxide radical generation potential of some common antibiotics. 2001, Pubmed
Rechsteiner, The biosynthesis and turnover of nicotinamide adenine dinucleotide in enucleated culture cells. 1974, Pubmed
Rizzi, Structural biology of enzymes involved in NAD and molybdenum cofactor biosynthesis. 2002, Pubmed
Rodgers, Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. 2005, Pubmed
Rongvaux, Reconstructing eukaryotic NAD metabolism. 2003, Pubmed
Ruddick, Tryptophan metabolism in the central nervous system: medical implications. 2006, Pubmed
Ryberg, Cerebrospinal fluid levels of free 3-nitrotyrosine are not elevated in the majority of patients with amyotrophic lateral sclerosis or Alzheimer's disease. 2004, Pubmed
Sablina, The antioxidant function of the p53 tumor suppressor. 2005, Pubmed
Sanni, Is ischemia involved in the pathogenesis of murine cerebral malaria? 2001, Pubmed
Schwarcz, The kynurenine pathway of tryptophan degradation as a drug target. 2004, Pubmed
Schweiger, Characterization of recombinant human nicotinamide mononucleotide adenylyl transferase (NMNAT), a nuclear enzyme essential for NAD synthesis. 2001, Pubmed
Seimiya, Tankyrase 1 as a target for telomere-directed molecular cancer therapeutics. 2005, Pubmed
Shi, SIRT3, a mitochondrial sirtuin deacetylase, regulates mitochondrial function and thermogenesis in brown adipocytes. 2005, Pubmed
Shi, Comparative studies of oxidative stress and mitochondrial function in aging. 2010, Pubmed
Sinclair, Toward a unified theory of caloric restriction and longevity regulation. 2005, Pubmed
Stone, Endogenous kynurenines as targets for drug discovery and development. 2002, Pubmed
Stone, The role of kynurenines in the production of neuronal death, and the neuroprotective effect of purines. 2001, Pubmed
Stone, Kynurenines in the CNS: from endogenous obscurity to therapeutic importance. 2001, Pubmed
Takikawa, Tryptophan degradation in mice initiated by indoleamine 2,3-dioxygenase. 1986, Pubmed
Tanaka, Cytometry of ATM activation and histone H2AX phosphorylation to estimate extent of DNA damage induced by exogenous agents. 2007, Pubmed
Uyttenhove, Evidence for a tumoral immune resistance mechanism based on tryptophan degradation by indoleamine 2,3-dioxygenase. 2003, Pubmed
Vakhrusheva, Sirt7-dependent inhibition of cell growth and proliferation might be instrumental to mediate tissue integrity during aging. 2008, Pubmed
WISS, [Splitting of kynurenine, oxykynurenine an related substances by the rat liver enzyme]. 1950, Pubmed
Wang, Apoptosis inducing factor and PARP-mediated injury in the MPTP mouse model of Parkinson's disease. 2003, Pubmed
Wang, Facilitation of glutamate release by nicotine involves the activation of a Ca2+/calmodulin signaling pathway in rat prefrontal cortex nerve terminals. 2006, Pubmed
Wielckens, DNA fragmentation and NAD depletion. Their relation to the turnover of endogenous mono(ADP-ribosyl) and poly(ADP-ribosyl) proteins. 1982, Pubmed
Ying, Poly(ADP-ribose) glycohydrolase mediates oxidative and excitotoxic neuronal death. 2001, Pubmed
Ying, NAD+ and NADH in brain functions, brain diseases and brain aging. 2007, Pubmed
Young, Decreased cADPR and increased NAD+ in the Cd38-/- mouse. 2006, Pubmed
Zhang, Are poly(ADP-ribosyl)ation by PARP-1 and deacetylation by Sir2 linked? 2003, Pubmed
Zhang, Nitric oxide activation of poly(ADP-ribose) synthetase in neurotoxicity. 1994, Pubmed
de Murcia, Requirement of poly(ADP-ribose) polymerase in recovery from DNA damage in mice and in cells. 1997, Pubmed
van der Veer, Extension of human cell lifespan by nicotinamide phosphoribosyltransferase. 2007, Pubmed
von Kobbe, Poly(ADP-ribose) polymerase 1 regulates both the exonuclease and helicase activities of the Werner syndrome protein. 2004, Pubmed