Skip to main content

Advertisement

SpringerLink
Log in

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

  • Published:
Journal of Bioenergetics and Biomembranes Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Asunción JG, Millan A, Pla R, Bruseguini I, Esteras A, Pallardo FV, Sastre J, Viña J (1996) FASEB J 10:333–338

    Google Scholar 

  • Ayala V, Naudí A, Sanz A, Caro P, portero-Otín M, Barja G, Pamplona R (2007) J Gerontol 62A:352–360

    CAS  Google Scholar 

  • Barja G (2004) Trends in Neurosci 27:595–600

    Article  CAS  Google Scholar 

  • Barja G, Herrero A (1998) J Bioenerg Biomembr 30:235–243

    Article  CAS  Google Scholar 

  • Benevenga NJ, Yeh MH, Lalich JJ (1976) J Nutr 106:1714–1720

    CAS  Google Scholar 

  • Boveris A, Cadenas E, Stoppani OM (1976) Biochem J 156:435–444

    CAS  Google Scholar 

  • Caro P, Gómez J, López-Torres M, Sanchez I, Naudí A, Jove M, Pamplona R, Barja G (2008) Biogerontology 9:183–196

    Article  CAS  Google Scholar 

  • 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 

  • Chang L, Zhao J, Xu J, Jiang W, Tang CS, Qi YF (2004) Clin Exp Pharmacol Physiol 31:237–243

    Article  CAS  Google Scholar 

  • Dever JT, Elfarra AA (2008) J Pharmacol Exp Therap 326:309–317

    Article  CAS  Google Scholar 

  • Fukagawa NK, Galbraith RA (2004) J Nutr 134:1569S–1574S

    CAS  Google Scholar 

  • Genova ML, Ventura B, Giulano G, Bovina C, Formiqqini G, Parenti Castelli G, Lenaz G (2001) FEBS Lett 505:364–368

    Article  CAS  Google Scholar 

  • Gómez J, Caro P, Naudí A, Portero-Otín M, Pamplona R, Barja G (2007) Biogerontology 8:555–566

    Article  CAS  Google Scholar 

  • Gomez-Cabrera M-C, Domenech E, Viña J (2008) Free Rad Biol Med 44:126–131

    Article  CAS  Google Scholar 

  • Gredilla R, Sanz A, López-Torres M, Barja G (2001a) FASEB J 15:1589–1591

    CAS  Google Scholar 

  • Gredilla R, Barja G, López-Torres M (2001b) J Bioenerg Biomembr 33:279–287

    Article  CAS  Google Scholar 

  • Guo Y-h, Chen F-y, Wang G-s, Chen L, Gao W (2008) Chinese Med J 121:2265–2271

    CAS  Google Scholar 

  • Harper AE, Benenga NJ, Wohlhueter RM (1970) Physiol Rev 50:428–558

    CAS  Google Scholar 

  • Hidiroglou N, Gilani GS, Long L, Zhao X, Madere R, Cockell K, Belonge B, Ratnayake WMN, Peace R (2004) J Nutr Biochem 15:730–740

    Article  CAS  Google Scholar 

  • Iwasaki K, Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, Yu BP (1988) J Gerontol 43:B13–B21

    CAS  Google Scholar 

  • Khorakova M, Deil Z, Khausman D, Matsek K (1990) Fisiol Zh 36:16–21

    CAS  Google Scholar 

  • Kudin AP, Debska-Vielhaber G, Kunz WS (2005) Biomed Pharmacother 59:163–168

    Article  CAS  Google Scholar 

  • Kumagai H, Katoh S, Hirosawa K, Kimura M, Hishida A, Ikegaya N (2002) Kidney Int 62:1219–1228

    Article  CAS  Google Scholar 

  • Labrune P, Perignon JL, Rault M, Brunet C, Lutun H, Charpentier C, Saudubray JM, Odievre M (1990) J Pediatr 117:220–226

    Article  CAS  Google Scholar 

  • Lambert AJ, Boysen HM, Buckingham JA, Yang T, Podlutsky A, Austad SN, Kunz TH, Buffenstein R, Brand MD (2007) Aging Cell 6:607–618

    Article  CAS  Google Scholar 

  • Latorre A, Moya A, Ayala A (1986) PNAS USA 83:8649–8653

    Article  CAS  Google Scholar 

  • Loft S, Poulsen HE (1999) Methods Enzymol 300:166–184

    Article  CAS  Google Scholar 

  • Lopez-Torres M, Barja G (2008a) Biochim Biophys Acta 1780:1337–1347

    CAS  Google Scholar 

  • 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. 149–162

  • Lopez-Torres M, Pérez-Campo R, Rojas C, Cadenas S, Barja G (1993) Free Rad Biol Med 15:133–142

    Article  CAS  Google Scholar 

  • Mair W, Piper MDW, Partridge L (2005) PLOS Biology 3:1305–1311

    Article  CAS  Google Scholar 

  • Malloy VL, Krajcik RA, Bailey SJ, Hristopoulos G, Plummer JD, Orentreich N (2006) Aging Cell 5:305–314

    Article  CAS  Google Scholar 

  • Mela L, Seitz S (1979) Methods Enzymol 55:39–46

    Article  CAS  Google Scholar 

  • Miller RA, Buehner G, Chang Y, Harper JM, Sigler R (2005) Aging Cell 4:119–125

    Article  CAS  Google Scholar 

  • Min KJ, Tatar M (2006) Mech Ageing Dev 127:643–646

    Article  CAS  Google Scholar 

  • Mori N, Hirayama K (2000) J Nutr 130:2349–2355

    CAS  Google Scholar 

  • Naudí A, Caro P, Jové M, Gómez J, Boada J, Ayala V, Portero-Otín M, Barja G, Pamplona R (2007) Rejuvenation Res 10:473–483

    Article  Google Scholar 

  • 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 44:437–445

    Article  Google Scholar 

  • Obeid R, Herrmann W (2006) FEBS Letters 580:2994–3005

    Article  CAS  Google Scholar 

  • Orentreich N, Matias JR, DeFelice A, Zimmerman JA (1993) J Nutr 123:269–274

    CAS  Google Scholar 

  • Pamplona R, Barja G (2006) Biochim Biophys Acta 1757:496–508

    Article  CAS  Google Scholar 

  • Pamplona R, Prat J, Cadenas S, Rojas C, Perez-Campo R, Lopez-Torres M, Barja G (1996) Mech Ageing Dev 53:53–66

    Article  Google Scholar 

  • Pamplona R, Barja G, Portero-Otín M (2002) Ann New York Acad Sci 959:475–490

    Article  CAS  Google Scholar 

  • Park CM, Cho CW, Rosenfeld ME, Song YS (2008) J Med Food 11:667–674

    Article  CAS  Google Scholar 

  • Porter AG, Urbano GL (2006) Bioessays 28:834–843

    Article  CAS  Google Scholar 

  • Regina M, Korhonen V-P, Smith TK, Alakuijala L, Eloranta TO (1993) Arch Biochem Biophys 300:598–607

    Article  CAS  Google Scholar 

  • Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA (1994) FASEB J 8:1302–1307

    CAS  Google Scholar 

  • Robert KA, Brunet-Rossini A, Bronikowski AM (2007) Aging Cell 6:395–404

    Article  CAS  Google Scholar 

  • 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. 183–189

  • Sanz A, Caro P, Barja G (2004) J Bioenerg Biomembr 36:545–552

    Article  CAS  Google Scholar 

  • Sanz A, Caro P, Gómez J, Barja G (2006a) Ann New York Acad Sci 1067:200–209

    Article  CAS  Google Scholar 

  • Sanz A, Gómez J, Caro P, Barja G (2006b) J Bioenerg Biomembr 38:327–333

    Article  CAS  Google Scholar 

  • Sanz A, Caro P, Ayala V, Portero-Otín M, Pamplona R, Barja G (2006c) FASEB J 20:1064–1073

    Article  CAS  Google Scholar 

  • Seneviratne CK, Li T, Khaper N, Singal PK (1999) Am J Physiol Heart Circ Physiol 277:H2124–2128

    CAS  Google Scholar 

  • Shimokawa I, Higami Y, Yu BP, Masoro EJ, Ikeda T (1996) Aging Clin Exp Res 8:254–262

    CAS  Google Scholar 

  • Stefanello FM, Chiarani F, Kurek AG, Wannmacher CMD, Wajner M, Wyse ATS (2005) Int J Devl Neuroscience 23:651–656

    Article  CAS  Google Scholar 

  • Stipanuk MH (2004) Annu Rev Nutr 24:539–577

    Article  CAS  Google Scholar 

  • Taylor ER, Hurrell F, Shannon RJ, Lin TK, Hirst J, Murphy MP (2003) J Biol Chem 278:19603–19610

    Article  CAS  Google Scholar 

  • Toborek M, Kopiecna-Grzebieniak E, Drózdz M, Wieczorek M (1996) Nutrition 12:534–537

    Article  CAS  Google Scholar 

  • Troen AM, Lutgens E, Smith DE, Rosenberg IH, Selhub J (2003) PNAS 100:15089–15094

    Article  CAS  Google Scholar 

  • Troen AM, French EE, Roberts JF, Selhub J, Ordovas JM, Parnell LD, Lai C-Q (2007) Age 29:29–39

    Article  CAS  Google Scholar 

  • Tyagi N, Moshal KS, Sen U, Vacek TP, Kumar M, Hughes WM, Kundu S, Tyagi SC (2009) Antioxidants and Redox Signaling 11:25–33

    Article  CAS  Google Scholar 

  • 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 23:4679–4689

    Article  CAS  Google Scholar 

  • Velez-Carrasco W, Merkel M, Twiss CO, Smith JD (2008) J Nutr Biochem 19:362–370

    Article  CAS  Google Scholar 

  • Verhoef P, van Vliet T, Olthof MR, Katan MB (2005) Am J Clin Nutr 82:553–558

    CAS  Google Scholar 

  • 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 107:1263–1273

    Article  CAS  Google Scholar 

  • Yokota F, Esashi T, Suzue R (1978) J Nutr Sci Vitaminol 24:527–533

    CAS  Google Scholar 

  • Zimmerman JA, Malloy V, Krajccik R, Orentreich N (2003) Exp Gerontol 38:47–52

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Animal Physiology II, Faculty of Biological Sciences, Complutense University, Madrid, 28040, Spain

    Jose Gomez, Pilar Caro, Ines Sanchez, Monica Lopez-Torres & Gustavo Barja

  2. Department of Experimental Medicine, Faculty of Medicine, University of Lleida-IRBLLEIDA, Lleida, 25008, Spain

    Alba Naudi, Mariona Jove, Manuel Portero-Otin & Reinald Pamplona

Authors
  1. Jose Gomez
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Pilar Caro
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ines Sanchez
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Alba Naudi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Mariona Jove
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Manuel Portero-Otin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Monica Lopez-Torres
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Reinald Pamplona
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Gustavo Barja
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gustavo Barja.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gomez, J., Caro, P., Sanchez, I. et al. Effect of methionine dietary supplementation on mitochondrial oxygen radical generation and oxidative DNA damage in rat liver and heart. J Bioenerg Biomembr 41, 309–321 (2009). https://doi.org/10.1007/s10863-009-9229-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10863-009-9229-3

Keywords

Search

Navigation