Journal of Bioenergetics and Biomembranes

, Volume 41, Issue 3, pp 309–321

Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and oxidative DNA damage in rat liver and heart

  • Jose Gomez
  • Pilar Caro
  • Ines Sanchez
  • Alba Naudi
  • Mariona Jove
  • Manuel Portero-Otin
  • Monica Lopez-Torres
  • Reinald Pamplona
  • Gustavo Barja
Article

Abstract

Methionine restriction without energy restriction increases, like caloric restriction, maximum longevity in rodents. Previous studies have shown that methionine restriction strongly decreases mitochondrial reactive oxygen species (ROS) production and oxidative damage to mitochondrial DNA, lowers membrane unsaturation, and decreases five different markers of protein oxidation in rat heart and liver mitochondria. It is unknown whether methionine supplementation in the diet can induce opposite changes, which is also interesting because excessive dietary methionine is hepatotoxic and induces cardiovascular alterations. Because the detailed mechanisms of methionine-related hepatotoxicity and cardiovascular toxicity are poorly understood and today many Western human populations consume levels of dietary protein (and thus, methionine) 2–3.3 fold higher than the average adult requirement, in the present experiment we analyze the effect of a methionine supplemented diet on mitochondrial ROS production and oxidative damage in the rat liver and heart mitochondria. In this investigation male Wistar rats were fed either a L-methionine-supplemented (2.5 g/100 g) diet without changing any other dietary components or a control (0.86 g/100 g) diet for 7 weeks. It was found that methionine supplementation increased mitochondrial ROS generation and percent free radical leak in rat liver mitochondria but not in rat heart. In agreement with these data oxidative damage to mitochondrial DNA increased only in rat liver, but no changes were observed in five different markers of protein oxidation in both organs. The content of mitochondrial respiratory chain complexes and AIF (apoptosis inducing factor) did not change after the dietary supplementation while fatty acid unsaturation decreased. Methionine, S-AdenosylMethionine and S-AdenosylHomocysteine concentration increased in both organs in the supplemented group. These results show that methionine supplementation in the diet specifically increases mitochondrial ROS production and mitochondrial DNA oxidative damage in rat liver mitochondria offering a plausible mechanism for its hepatotoxicity.

Keywords

Methionine supplementation Free radicals Aging ROS Oxidative stress Mitochondria DNA damage 

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References

  1. Asunción JG, Millan A, Pla R, Bruseguini I, Esteras A, Pallardo FV, Sastre J, Viña J (1996) FASEB J 10:333–338Google Scholar
  2. Ayala V, Naudí A, Sanz A, Caro P, portero-Otín M, Barja G, Pamplona R (2007) J Gerontol 62A:352–360Google Scholar
  3. Barja G (2004) Trends in Neurosci 27:595–600CrossRefGoogle Scholar
  4. Barja G, Herrero A (1998) J Bioenerg Biomembr 30:235–243CrossRefGoogle Scholar
  5. Benevenga NJ, Yeh MH, Lalich JJ (1976) J Nutr 106:1714–1720Google Scholar
  6. Boveris A, Cadenas E, Stoppani OM (1976) Biochem J 156:435–444Google Scholar
  7. Caro P, Gómez J, López-Torres M, Sanchez I, Naudí A, Jove M, Pamplona R, Barja G (2008) Biogerontology 9:183–196CrossRefGoogle Scholar
  8. Caro P, Gomez J, Sanchez I, Garcia R, Lopez-Torres M, Naudí A, Portero-Otin M, Pamplona R, Barja G (2009) Biogerontology . doi:10.1007/s10522-008-9200-4 Google Scholar
  9. Chang L, Zhao J, Xu J, Jiang W, Tang CS, Qi YF (2004) Clin Exp Pharmacol Physiol 31:237–243CrossRefGoogle Scholar
  10. Dever JT, Elfarra AA (2008) J Pharmacol Exp Therap 326:309–317CrossRefGoogle Scholar
  11. Fukagawa NK, Galbraith RA (2004) J Nutr 134:1569S–1574SGoogle Scholar
  12. Genova ML, Ventura B, Giulano G, Bovina C, Formiqqini G, Parenti Castelli G, Lenaz G (2001) FEBS Lett 505:364–368CrossRefGoogle Scholar
  13. Gómez J, Caro P, Naudí A, Portero-Otín M, Pamplona R, Barja G (2007) Biogerontology 8:555–566CrossRefGoogle Scholar
  14. Gomez-Cabrera M-C, Domenech E, Viña J (2008) Free Rad Biol Med 44:126–131CrossRefGoogle Scholar
  15. Gredilla R, Sanz A, López-Torres M, Barja G (2001a) FASEB J 15:1589–1591Google Scholar
  16. Gredilla R, Barja G, López-Torres M (2001b) J Bioenerg Biomembr 33:279–287CrossRefGoogle Scholar
  17. Guo Y-h, Chen F-y, Wang G-s, Chen L, Gao W (2008) Chinese Med J 121:2265–2271Google Scholar
  18. Harper AE, Benenga NJ, Wohlhueter RM (1970) Physiol Rev 50:428–558Google Scholar
  19. Hidiroglou N, Gilani GS, Long L, Zhao X, Madere R, Cockell K, Belonge B, Ratnayake WMN, Peace R (2004) J Nutr Biochem 15:730–740CrossRefGoogle Scholar
  20. Iwasaki K, Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, Yu BP (1988) J Gerontol 43:B13–B21Google Scholar
  21. Khorakova M, Deil Z, Khausman D, Matsek K (1990) Fisiol Zh 36:16–21Google Scholar
  22. Kudin AP, Debska-Vielhaber G, Kunz WS (2005) Biomed Pharmacother 59:163–168CrossRefGoogle Scholar
  23. Kumagai H, Katoh S, Hirosawa K, Kimura M, Hishida A, Ikegaya N (2002) Kidney Int 62:1219–1228CrossRefGoogle Scholar
  24. Labrune P, Perignon JL, Rault M, Brunet C, Lutun H, Charpentier C, Saudubray JM, Odievre M (1990) J Pediatr 117:220–226CrossRefGoogle Scholar
  25. Lambert AJ, Boysen HM, Buckingham JA, Yang T, Podlutsky A, Austad SN, Kunz TH, Buffenstein R, Brand MD (2007) Aging Cell 6:607–618CrossRefGoogle Scholar
  26. Latorre A, Moya A, Ayala A (1986) PNAS USA 83:8649–8653CrossRefGoogle Scholar
  27. Loft S, Poulsen HE (1999) Methods Enzymol 300:166–184CrossRefGoogle Scholar
  28. Lopez-Torres M, Barja G (2008a) Biochim Biophys Acta 1780:1337–1347Google Scholar
  29. Lopez-Torres M, Barja G (2008b). In Oxidative Stress in Aging. From model systems to human diseases: Mitochondrial Free Radical Production and Caloric Restriction: Implications in vertebrate Longevity and Aging (Miwa S, Beckman KB and Muller FL, eds.), Humana Press, pp. 149–162Google Scholar
  30. Lopez-Torres M, Pérez-Campo R, Rojas C, Cadenas S, Barja G (1993) Free Rad Biol Med 15:133–142CrossRefGoogle Scholar
  31. Mair W, Piper MDW, Partridge L (2005) PLOS Biology 3:1305–1311CrossRefGoogle Scholar
  32. Malloy VL, Krajcik RA, Bailey SJ, Hristopoulos G, Plummer JD, Orentreich N (2006) Aging Cell 5:305–314CrossRefGoogle Scholar
  33. Mela L, Seitz S (1979) Methods Enzymol 55:39–46CrossRefGoogle Scholar
  34. Miller RA, Buehner G, Chang Y, Harper JM, Sigler R (2005) Aging Cell 4:119–125CrossRefGoogle Scholar
  35. Min KJ, Tatar M (2006) Mech Ageing Dev 127:643–646CrossRefGoogle Scholar
  36. Mori N, Hirayama K (2000) J Nutr 130:2349–2355Google Scholar
  37. Naudí A, Caro P, Jové M, Gómez J, Boada J, Ayala V, Portero-Otín M, Barja G, Pamplona R (2007) Rejuvenation Res 10:473–483CrossRefGoogle Scholar
  38. Ninomiya T, Kiyohara Y, Kubo M, Tanizaki Y, Tanak K, Okubo K, Nakamura H, Hata J, Oishi Y, Kato I, Hirakata H, Lida M (2004) Am J Kidney Dis 44:437–445CrossRefGoogle Scholar
  39. Obeid R, Herrmann W (2006) FEBS Letters 580:2994–3005CrossRefGoogle Scholar
  40. Orentreich N, Matias JR, DeFelice A, Zimmerman JA (1993) J Nutr 123:269–274Google Scholar
  41. Pamplona R, Barja G (2006) Biochim Biophys Acta 1757:496–508CrossRefGoogle Scholar
  42. Pamplona R, Prat J, Cadenas S, Rojas C, Perez-Campo R, Lopez-Torres M, Barja G (1996) Mech Ageing Dev 53:53–66CrossRefGoogle Scholar
  43. Pamplona R, Barja G, Portero-Otín M (2002) Ann New York Acad Sci 959:475–490CrossRefGoogle Scholar
  44. Park CM, Cho CW, Rosenfeld ME, Song YS (2008) J Med Food 11:667–674CrossRefGoogle Scholar
  45. Porter AG, Urbano GL (2006) Bioessays 28:834–843CrossRefGoogle Scholar
  46. Regina M, Korhonen V-P, Smith TK, Alakuijala L, Eloranta TO (1993) Arch Biochem Biophys 300:598–607CrossRefGoogle Scholar
  47. Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA (1994) FASEB J 8:1302–1307Google Scholar
  48. Robert KA, Brunet-Rossini A, Bronikowski AM (2007) Aging Cell 6:395–404CrossRefGoogle Scholar
  49. Sanz A, Barja G (2006) In Handbook of Models for Human Aging: Estimation of the rate of production of oxygen free radicals by mitochondria (Conn M ed.) Academic Press, pp. 183–189Google Scholar
  50. Sanz A, Caro P, Barja G (2004) J Bioenerg Biomembr 36:545–552CrossRefGoogle Scholar
  51. Sanz A, Caro P, Gómez J, Barja G (2006a) Ann New York Acad Sci 1067:200–209CrossRefGoogle Scholar
  52. Sanz A, Gómez J, Caro P, Barja G (2006b) J Bioenerg Biomembr 38:327–333CrossRefGoogle Scholar
  53. Sanz A, Caro P, Ayala V, Portero-Otín M, Pamplona R, Barja G (2006c) FASEB J 20:1064–1073CrossRefGoogle Scholar
  54. Seneviratne CK, Li T, Khaper N, Singal PK (1999) Am J Physiol Heart Circ Physiol 277:H2124–2128Google Scholar
  55. Shimokawa I, Higami Y, Yu BP, Masoro EJ, Ikeda T (1996) Aging Clin Exp Res 8:254–262Google Scholar
  56. Stefanello FM, Chiarani F, Kurek AG, Wannmacher CMD, Wajner M, Wyse ATS (2005) Int J Devl Neuroscience 23:651–656CrossRefGoogle Scholar
  57. Stipanuk MH (2004) Annu Rev Nutr 24:539–577CrossRefGoogle Scholar
  58. Taylor ER, Hurrell F, Shannon RJ, Lin TK, Hirst J, Murphy MP (2003) J Biol Chem 278:19603–19610CrossRefGoogle Scholar
  59. Toborek M, Kopiecna-Grzebieniak E, Drózdz M, Wieczorek M (1996) Nutrition 12:534–537CrossRefGoogle Scholar
  60. Troen AM, Lutgens E, Smith DE, Rosenberg IH, Selhub J (2003) PNAS 100:15089–15094CrossRefGoogle Scholar
  61. Troen AM, French EE, Roberts JF, Selhub J, Ordovas JM, Parnell LD, Lai C-Q (2007) Age 29:29–39CrossRefGoogle Scholar
  62. Tyagi N, Moshal KS, Sen U, Vacek TP, Kumar M, Hughes WM, Kundu S, Tyagi SC (2009) Antioxidants and Redox Signaling 11:25–33CrossRefGoogle Scholar
  63. Vahsen N, Candé C, Brière JJ, Bénit P, Joza N, Larochette N, Mastroberardino PG, Pequignot MO, Casares N, Lazar V, Feraud O, Debili N, Wissing S, Engelhardt S, Madeo F, Piacentini M, Penninger JM, Schägger H, Rustin P, Kroemer G (2004) EMBO J 23:4679–4689CrossRefGoogle Scholar
  64. Velez-Carrasco W, Merkel M, Twiss CO, Smith JD (2008) J Nutr Biochem 19:362–370CrossRefGoogle Scholar
  65. Verhoef P, van Vliet T, Olthof MR, Katan MB (2005) Am J Clin Nutr 82:553–558Google Scholar
  66. Werstuck GH, Lentz SR, Dayal S, Hossain GS, Sood SK, Shi YY, Zhou J, Maeda N, Krisans SK, Malinow MR, Austin RC (2001) J Clin Invest 107:1263–1273CrossRefGoogle Scholar
  67. Yokota F, Esashi T, Suzue R (1978) J Nutr Sci Vitaminol 24:527–533Google Scholar
  68. Zimmerman JA, Malloy V, Krajccik R, Orentreich N (2003) Exp Gerontol 38:47–52CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  • Jose Gomez
    • 1
  • Pilar Caro
    • 1
  • Ines Sanchez
    • 1
  • Alba Naudi
    • 2
  • Mariona Jove
    • 2
  • Manuel Portero-Otin
    • 2
  • Monica Lopez-Torres
    • 1
  • Reinald Pamplona
    • 2
  • Gustavo Barja
    • 1
  1. 1.Department of Animal Physiology II, Faculty of Biological SciencesComplutense UniversityMadridSpain
  2. 2.Department of Experimental Medicine, Faculty of MedicineUniversity of Lleida-IRBLLEIDALleidaSpain

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