Metabolomic analysis of exercise effects in the POLG mitochondrial DNA mutator mouse brain

Neurobiology of Aging

Volumn 36, Issue 11, 2015, Pages 2972-2983

  Clark Matott, Joanne ^a   Saleem, Ayesha ^b   Dai, Ying ^a   Shurubor, Yevgeniya ^c   Ma, Xiaoxing ^b   Safdar, Adeel ^a   Beal, Myron Flint ^c   Tarnopolsky, Mark ^b   Simon, David K ^a  

^a HARVARD MEDICAL SCHOOL   (United States)

^b MCMASTER UNIVERSITY MEDICAL CENTRE   (Canada)

^c WEILL CORNELL MEDICAL COLLEGE   (United States)

Author keywords

Aging; DNA damage; Exercise; Metabolism; Mitochondria; NAD

Indexed keywords

ACETYL COENZYME A; ACETYLCHOLINE; ASPARTIC ACID; CARNITINE; CITICOLINE; GLUTAMIC ACID; MITOCHONDRIAL DNA; NICOTINAMIDE ADENINE DINUCLEOTIDE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE 1; THIONEINE; AGENTS INTERACTING WITH TRANSMITTER, HORMONE OR DRUG RECEPTORS; ANTIOXIDANT; DNA DIRECTED DNA POLYMERASE; GLUTAMIC ACID DERIVATIVE; NICOTINAMIDE ADENINE DINUCLEOTIDE ADENOSINE DIPHOSPHATE RIBOSYLTRANSFERASE; PARP1 PROTEIN, MOUSE; POLG PROTEIN, MOUSE;

ACETYLCHOLINE BRAIN LEVEL; AMINO ACID BRAIN LEVEL; AMINO ACID METABOLISM; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BRAIN CORTEX; CHOLINERGIC TRANSMISSION; CONTROLLED STUDY; ENDURANCE TRAINING; ENZYME ACTIVITY; EXPLORATORY RESEARCH; FEMALE; GLUTAMATERGIC NEUROTRANSMISSION; MALE; METABOLOMICS; MOUSE; NEUROTRANSMISSION; NONHUMAN; PRIORITY JOURNAL; SEDENTARY LIFESTYLE; SOMATIC MUTATION; TREADMILL EXERCISE; UPREGULATION; AGING; ANIMAL; BRAIN; DNA DAMAGE; GENETICS; METABOLISM; MUTATION;

ACETYLCHOLINE; AGING; ANIMALS; ANTIOXIDANTS; ASPARTIC ACID; BRAIN; CARNITINE; DNA DAMAGE; DNA, MITOCHONDRIAL; DNA-DIRECTED DNA POLYMERASE; FEMALE; GLUTAMATES; MALE; METABOLOMICS; MICE; MUTATION; NAD; NEUROTRANSMITTER AGENTS; PHYSICAL CONDITIONING, ANIMAL; POLY (ADP-RIBOSE) POLYMERASE-1; POLY(ADP-RIBOSE) POLYMERASES;

EID: 84947045067     PISSN: 01974580     EISSN: 15581497     Source Type: Journal    
DOI: 10.1016/j.neurobiolaging.2015.07.020     Document Type: Article

References (66)

1. Alano C.C., Garnier P., Ying W., Higashi Y., Kauppinen T.M., Swanson R.A. NAD+ depletion is necessary and sufficient for poly(ADP-ribose) polymerase-1-mediated neuronal death. J. Neurosci. 2010, 30:2967-2978.
2. Bellia F., Calabrese V., Guarino F., Cavallaro M., Cornelius C., De Pinto V., Rizzarelli E. Carnosinase levels in aging brain: redox state induction and cellular stress response. Antioxid. Redox Signal. 2009, 11:2759-2775.
3. Berger N.A. Poly(ADP-ribose) in the cellular response to DNA damage. Radiat. Res. 1985, 101:4-15.
4. Boudonck K.J., Mitchell M.W., Nemet L., Keresztes L., Nyska A., Shinar D., Rosenstock M. Discovery of metabolomics biomarkers for early detection of nephrotoxicity. Toxicologic Pathol. 2009, 37:280-292.
5. Cheng K.C., Cahill D.S., Kasai H., Nishimura S., Loeb L.A. 8-Hydroxyguanine, an abundant form of oxidative DNA damage, causes G---T and A---C substitutions. J. Biol. Chem. 1992, 267:166-172.
6. Clark J., Dai Y., Simon D.K. Do somatic mitochondrial DNA mutations contribute to Parkinson's disease?. Parkinsons Dis. 2011, 2011:659694.
7. Clark J., Silvaggi J.M., Kiselak T., Zheng K., Clore E.L., Dai Y., Bass C.E., Simon D.K. Pgc-1α overexpression downregulates Pitx3 and increases susceptibility to MPTP toxicity associated with decreased Bdnf. PLoS One 2012, 7:e48925.
8. Currais A., Maher P. Functional consequences of age-dependent changes in glutathione status in the brain. Antioxid. Redox Signal. 2013, 19:813-822.
9. Daft F.S., Kornberg A. Anemia and granulocytopenia in rats fed a diet low in pantothenic acid. Public Health Rep. 1945, 60:1201-1215.
10. Dai D.-F., Chen T., Wanagat J., Laflamme M., Marcinek D.J., Emond M.J., Ngo C.P., Prolla T.A., Rabinovitch P.S. Age-dependent cardiomyopathy in mitochondrial mutator mice is attenuated by overexpression of catalase targeted to mitochondria. Aging Cell 2010, 9:536-544.
11. Dai Y., Kiselak T., Clark J., Clore E., Zheng K., Cheng A., Kujoth G.C., Prolla T.A., Maratos-Flier E., Simon D.K. Behavioral and metabolic characterization of heterozygous and homozygous POLG mutator mice. Mitochondrion 2013, 13:1-10.
12. DeHaven C.D., Evans A.M., Dai H., Lawton K.A. Organization of GC/MS and LC/MS metabolomics data into chemical libraries. J. Cheminformatics 2010, 2:9.
13. Emir U.E., Raatz S., McPherson S., Hodges J.S., Torkelson C., Tawfik P., White T., Terpstra M. Noninvasive quantification of ascorbate and glutathione concentration in the elderly human brain. NMR Biomed. 2011, 24:888-894.
14. Enokido Y. Cystathionine -synthase, a key enzyme for homocysteine metabolism, is preferentially expressed in the radial glia/astrocyte lineage of developing mouse CNS. FASEB J. 2005, 19:1854-1856.
15. Everaert I., Mooyaart A., Baguet A., Zutinic A., Baelde H., Achten E., Taes Y., De Heer E., Derave W. Vegetarianism, female gender and increasing age, but not CNDP1 genotype, are associated with reduced muscle carnosine levels in humans. Amino Acids 2010, 40:1221-1229.
16. Fox R.G., Magness S., Kujoth G.C., Prolla T.A., Maeda N. Mitochondrial DNA polymerase editing mutation, PolgD257A, disturbs stem-progenitor cell cycling in the small intestine and restricts excess fat absorption. Am. J. Physiol Gastrointest. Liver Physiol. 2012, 302:G914-G924.
17. Friedlander A.L., Casazza G.A., Horning M.A., Buddinger T.F., Brooks G.A. Effects of exercise intensity and training on lipid metabolism in young women. Am. J. Physiol. 1998, 275:E853-E863.
18. García-Espinosa M.A., Rodrigues T.B., Sierra A., Benito M., Fonseca C., Gray H.L., Bartnik B.L., García-Martín M.L., Ballesteros P., Cerdan S. Cerebral glucose metabolism and the glutamine cycle as detected by in vivo and in vitro 13C NMR spectroscopy. Neurochem. Int. 2004, 45:297-303.
19. Gomes A.P., Price N.L., Ling A.J.Y., Moslehi J.J., Montgomery M.K., Rajman L., White J.P., Teodoro J.S., Wrann C.D., Hubbard B.P., Mercken E.M., Palmeira C.M., de Cabo R., Rolo A.P., Turner N., Bell E.L., Sinclair D.A. Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell 2013, 155:1624-1638.
20. Gueli M.C., Taibi G. Alzheimer's disease: amino acid levels and brain metabolic status. Neurol. Sci. 2013, 34:1575-1579.
21. Hawkins R.A. The blood-brain barrier and glutamate. Am. J. Clin. Nutr. 2009, 90:867S-874S.
22. Hill E., Kalloniatis M., Tan S.S. Glutamate, GABA and precursor amino acids in adult mouse neocortex: cellular diversity revealed by quantitative immunocytochemistry. Cereb. Cortex 2000, 10:1132-1142.
23. Hiona A., Sanz A., Kujoth G.C., Pamplona R., Seo A.Y., Hofer T., Someya S., Miyakawa T., Nakayama C., Samhan-Arias A.K., Servais S., Barger J.L., Portero-Otín M., Tanokura M., Prolla T.A., Leeuwenburgh C. Mitochondrial DNA mutations induce mitochondrial dysfunction, apoptosis and sarcopenia in skeletal muscle of mitochondrial DNA mutator mice. PLoS One 2010, 5:e11468.
24. Hipkiss A.R. Aging, proteotoxicity, mitochondria, glycation, NAD+ and carnosine: possible inter-relationships and resolution of the oxygen paradox. Front. Aging Neurosci. 2010, 2:10.
25. Infante J.P. Impaired glycerophosphorylcholine synthesis in murine muscular dystrophy. Med. Biol. 1985, 2:81-87.
26. Infante J.P., Huszagh V.A. Secondary carnitine deficiency and impaired docosahexaenoic (22:6 n-3) acid synthesis: a common denominator in the pathophysiology of diseases of oxidative phosphorylation and β-oxidation. FEBS Lett. 2000, 468:1-5.
27. Johnson A.A., Johnson K.A. Exonuclease proofreading by human mitochondrial DNA polymerase. J. Biol. Chem. 2001, 276:38097-38107.
28. Kilpatrick E.S.E., Keevilt B.G.B., Richmond K.L.K., Newland P.P., Addison G.M.G. Plasma 1,5-anhydroglucitol concentrations are influenced by variations in the renal threshold for glucose. Diabet Med. 1999, 16:496-499.
29. Kim H.-Y., Akbar M., Lau A. Effects of docosapentaenoic acid on neuronal apoptosis. Lipids 2003, 38:453-457.
30. Kolesar J.E., Safdar A., Abadi A., Mac Neil L.G., Crane J.D., Tarnopolsky M.A., Kaufman B.A. Defects in mitochondrial DNA replication and oxidative damage in muscle of mtDNA mutator mice. Free Radic. Biol. Med. 2014, 75:241-251.
31. Kraytsberg Y., Simon D.K., Turnbull D.M., Khrapko K. Do mtDNA deletions drive premature aging in mtDNA mutator mice?. Aging Cell 2009, 8:502-506.
32. Krebs H.A., Veech R.L. Equilibrium relations between pyridine nucleotides and adenine nucleotides and their roles in the regulation of metabolic processes. Adv. Enzyme Regul. 1969, 7:397-413.
33. Krishnan K.J., Reeve A.K., Samuels D.C., Chinnery P.F., Blackwood J.K., Taylor R.W., Wanrooij S., Spelbrink J.N., Lightowlers R.N., Turnbull D.M. What causes mitochondrial DNA deletions in human cells?. Nat. Genet. 2008, 40:275-279.
34. Kuchino Y., Mori F., Kasai H., Inoue H., Iwai S., Miura K., Ohtsuka E., Nishimura S. Misreading of DNA templates containing 8-hydroxydeoxyguanosine at the modified base and at adjacent residues. Nature 1987, 327:77-79.
35. Kujoth G.C., Hiona A., Pugh T.D., Someya S., Panzer K., Wohlgemuth S.E., Hofer T., Seo A.Y., Sullivan R., Jobling W.A., Morrow J.D., Van Remmen H., Sedivy J.M., Yamasoba T., Tanokura M., Weindruch R., Leeuwenburgh C., Prolla T. Mitochondrial DNA mutations, oxidative stress, and apoptosis in mammalian aging. Science 2005, 309:481-484.
36. Kuo Y.M., Hayflick S.J., Gitschier J. Deprivation of pantothenic acid elicits a movement disorder and azoospermia in a mouse model of pantothenate kinase-associated neurodegeneration. J. Inherit. Metab. Dis. 2007, 30:310-317.
37. Lawton K.A., Berger A., Mitchell M., Milgram K.E., Evans A.M., Guo L., Hanson R.W., Kalhan S.C., Ryals J.A., Milburn M.V. Analysis of the adult human plasma metabolome. Pharmacogenomics 2008, 9:383-397.
38. Lin M.T., Castelvetri I.C., Zheng K.K., Jackson K.E., Tan Y.B., Arzberger T., Lees A.J., Betensky R.A., Beal M.F., Simon D.K. Somatic mitochondrial DNA mutations in early Parkinson and incidental Lewy body disease. Ann. Neurol. 2012, 71:850-854.
39. Lin M.T., Simon D.K., Ahn C.H., Kim L.M., Beal M.F. High aggregate burden of somatic mtDNA point mutations in aging and Alzheimer's disease brain. Hum. Mol. Genet. 2002, 11:133-145.
40. Llanos A., Li Y., Mena P., Salem N., Uauy R. Infants with intrauterine growth restriction have impaired formation of docosahexaenoic acid in early neonatal life: a stable isotope study. Pediatr. Res. 2005, 58:735-740.
41. Logan A., Shabalina I.G., Prime T.A., Rogatti S., Kalinovich A.V., Hartley R.C., Budd R.C., Cannon B., Murphy M.P. In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice. Aging Cell 2014, 13:765-768.
42. Love S. Increased poly(ADP-ribosyl)ation of nuclear proteins in Alzheimer's disease. Brain 1999, 122:247-253.
43. McClay J.L., Adkins D.E., Vunck S.A., Batman A.M., Vann R.E., Clark S.L., Beardsley P.M., van den Oord E.J. Large-scale neurochemical metabolomics analysis identifies multiple compounds associated with methamphetamine exposure. Metabolomics 2012, 9:392-402.
44. Mecocci P., Beal M.F., Cecchetti R., Polidori M., Cherubini A., Chionne F., Avelini L., Romano G., Senin U. Mitochondrial membrane fluidity and oxidative damage to mitochondrial DNA in aged and AD human brain. Mol. Chem. Neuropathol. 1997, 31:63-74.
45. Mingorance C., Rodriguez-Rodriguez R., Justo M.L., Herrera M.D., de Sotomayor M.A. Pharmacological effects and clinical applications of propionyl-L-carnitine. Nutr. Rev. 2011, 69:279-290.
46. Mousavi M., Jonsson P., Antti H., Adolfsson R., Nordin A., Bergdahl J., Eriksson K., Moritz T., Nilsson L.-G., Nyberg L. Serum metabolomic biomarkers of dementia. Dement. Geriatr. Cogn. Dis. Extra 2014, 4:252-262.
47. Ribas G.S., Vargas C.R., Wajner M. l-carnitine supplementation as a potential antioxidant therapy for inherited neurometabolic disorders. Gene 2014, 533:469-476.
48. Riederer P., Hoyer S. From benefit to damage. Glutamate and advanced glycation end products in Alzheimer brain. J. Neural Transm. 2006, 113:1671-1677.
49. Rossi M.N., Carbone M., Mostocotto C., Mancone C., Tripodi M., Maione R., Amati P. Mitochondrial localization of PARP-1 requires interaction with mitofilin and is involved in the maintenance of mitochondrial DNA integrity. J. Biol. Chem. 2009, 284:31616-31624.
50. Safdar A., Bourgeois J.M., Ogborn D.I., Little J.P., Hettinga B.P., Akhtar M., Thompson J.E., Melov S., Mocellin N.J., Kujoth G.C., Prolla T.A., Tarnopolsky M.A. Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice. Proc. Natl. Acad. Sci. U. S. A. 2011, 108:4135-4140.
51. Safdar A., Little J.P., Stokl A.J., Hettinga B.P., Akhtar M., Tarnopolsky M.A. Exercise increases mitochondrial PGC-1 content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J. Biol. Chem. 2011, 286:10605-10617.
52. Saleem A., Safdar A., Kitaoka Y., Ma X., Marquez O.S., Akhtar M., Nazli A., Suri R., Turnbull J., Tarnopolsky M.A. Polymerase gamma mutator mice rely on increased glycolytic flux for energy production. Mitochondrion 2015, 21:19-26.
53. Saper C.B., Scammell T.E., Lu J. Hypothalamic regulation of sleep and circadian rhythms. Nature 2005, 437:1257-1263.
54. Schliebs R., Arendt T. The cholinergic system in aging and neuronal degeneration. Behav. Brain Res. 2011, 221:555-563.
55. Schnaar R.L., Gerardy-Schahn R., Hildebrandt H. Sialic acids in the brain: gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration. Physiol. Rev. 2014, 94:461-518.
56. Scholte H.R., Busch H.F., Luyt-Houwen I.E., Vaandrager-Verduin M.H., Przyrembel H., Arts W.F. Defects in oxidative phosphorylation. Biochemical investigations in skeletal muscle and expression of the lesion in other cells. J. Inherit. Metab. Dis. 1987, 10(Suppl 1):81-97.
57. Shah G.M., Kandan-Kulangara F., Montoni A., Shah R.G., Brind'Amour J., Vodenicharov M.D., Affar E.B. Approaches to detect PARP-1 activation in vivo, in situ, and in vitro. Methods Mol. Biol. 2011, 780:3-34.
58. Sreekumar A., Poisson L.M., Rajendiran T.M., Khan A.P., Cao Q., Yu J., Laxman B., Mehra R., Lonigro R.J., Li Y., Nyati M.K., Ahsan A., Kalyana-Sundaram S., Han B., Cao X., Byun J., Omenn G.S., Ghosh D., Pennathur S., Alexander D.C., Berger A., Shuster J.R., Wei J.T., Varambally S., Beecher C., Chinnaiyan A.M. Nature 2009, 457:910-914.
59. Stein L.R., Wozniak D.F., Dearborn J.T., Kubota S., Apte R.S., Izumi Y., Zorumski C.F., Imai S.I. Expression of nampt in hippocampal and cortical excitatory neurons is critical for cognitive function. J. Neurosci. 2014, 34:5800-5815.
60. Storey J.D., Tibshirani R. Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. U. S. A. 2003, 100:9440-9445.
61. Stuart J.A., Brown M.F. Mitochondrial DNA maintenance and bioenergetics. Biochim. Biophys. Acta 2006, 1757:79-89.
62. Trifunovic A., Wredenberg A., Falkenberg M., Spelbrink J.N., Rovio A.T., Bruder C.E., Bohlooly-Y M., Gidlof S., Oldfors A., Wiborn R., Tornell J., Jacobs H.T., Larsson N.-G. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 2004, 429:417-423.
63. Vermulst M., Wanagat J., Kujoth G.C., Bielas J.H., Rabinovitch P.S., Prolla T.A., Loeb L.A. DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice. Nat. Genet. 2008, 40:392-394.
64. Wallace D.C. A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Genetics 2005, 39:359-407.
65. Woolf N.J., Butcher L.L. Cholinergic systems mediate action from movement to higher consciousness. Behav. Brain Res. 2011, 221:488-498.
66. Yakes F.M., Van Houten B. Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress. Proc. Natl. Acad. Sci. U. S. A. 1997, 94:514-519.