Advertisement

AGE

, Volume 34, Issue 2, pp 389–403 | Cite as

Mediterranean diet supplemented with coenzyme Q10 induces postprandial changes in p53 in response to oxidative DNA damage in elderly subjects

  • Francisco M. Gutierrez-Mariscal
  • Pablo Perez-Martinez
  • Javier Delgado-Lista
  • Elena M. Yubero-Serrano
  • Antonio Camargo
  • Nieves Delgado-Casado
  • Cristina Cruz-Teno
  • Monica Santos-Gonzalez
  • Fernando Rodriguez-Cantalejo
  • Justo P. Castaño
  • Jose M. Villalba-Montoro
  • Francisco Fuentes
  • Francisco Perez-Jimenez
  • Jose Lopez-MirandaEmail author
Article

Abstract

Coenzyme Q10 (CoQ) is a powerful antioxidant that reduces oxidative stress. We explored whether the quality of dietary fat alters postprandial oxidative DNA damage and whether supplementation with CoQ improves antioxidant capacity by modifying the activation/stabilization of p53 in elderly subjects. In this crossover study, 20 subjects were randomly assigned to receive three isocaloric diets during 4 weeks each: (1) Mediterranean diet (Med diet), (2) Mediterranean diet supplemented with CoQ (Med+CoQ diet), and (3) saturated fatty acid-rich diet (SFA diet). Levels of mRNAs were determined for p53, p21, p53R2, and mdm2. Protein levels of p53, phosphorylated p53 (Ser20), and monoubiquitinated p53 were also measured, both in cytoplasm and nucleus. The extent of DNA damage was measured as plasma 8-OHdG. SFA diet displayed higher postprandial 8-OHdG concentrations, p53 mRNA and monoubiquitinated p53, and lower postprandial Mdm2 mRNA levels compared with Med and Med+CoQ diets (p < 0.05). Moreover, Med+CoQ diet induced a postprandial decrease of cytoplasmatic p53, nuclear p-p53 (Ser20), and nuclear and cytoplasmatic monoubiquitinated p53 protein (p < 0.05). In conclusion, Med+CoQ diet improves oxidative DNA damage in elderly subjects and reduces processes of cellular oxidation. Our results suggest a starting point for the prevention of oxidative processes associated with aging.

Keywords

Aging Coenzyme Q10 p53 Oxidative stress DNA damage 

Abbreviations

Apo

Apolipoprotein

BMI

Body mass index

CoQ

Coenzyme Q10

HDL-C

HDL cholesterol

LDL

Low-density lipoprotein

Med diet

Mediterranean diet

Med+CoQ diet

Mediterranean diet supplemented with CoQ

MUFA

Monounsaturated fatty acid

PUFA

Polyunsaturated fatty acid

ROS

Reactive oxygen species

SFA

Saturated fatty acid

SFA diet

Saturated fatty acid-rich diet

Notes

Acknowledgments

Source of support

This study was supported in part by research grants from the Ministerio de Ciencia e Innovación (AGL 2004-07907, AGL2006-01979, AGL2009-12270 to JL-M; CB06/03/0047-CIBER Fisiopatologia de la Obesidad y Nutrition is an initiative of ISCIII to FP-J), Consejería de Innovación, Ciencia y Empresa, Junta de Andalucía (P06-CTS-01425 to JL-M), Consejería de Salud, Junta de Andalucía (06/128, 07/43, PI0193/2009 to JL-M, 06/129 to FP-J), and Kaneka Corporation (Japan) for the production of CoQ and placebo capsules.

References

  1. Appella E, Anderson CW (2001) Post-translational modifications and activation of p53 by genotoxic stresses. Eur J Biochem 268(10):2764–2772PubMedCrossRefGoogle Scholar
  2. Ashcroft M, Taya Y, Vousden KH (2000) Stress signals utilize multiple pathways to stabilize p53. Mol Cell Biol 20(9):3224–3233PubMedCrossRefGoogle Scholar
  3. Bello RI, Gomez-Diaz C, Buron MI, Alcain FJ, Navas P, Villalba JM (2005) Enhanced anti-oxidant protection of liver membranes in long-lived rats fed on a coenzyme Q10-supplemented diet. Exp Gerontol 40(8–9):694–706PubMedCrossRefGoogle Scholar
  4. Bennett MR (2001) Reactive oxygen species and death: oxidative DNA damage in atherosclerosis. Circ Res 88(7):648–650PubMedCrossRefGoogle Scholar
  5. Bonora E, Corrao G, Bagnardi V, Ceriello A, Comaschi M, Montanari P, Meigs JB (2006) Prevalence and correlates of post-prandial hyperglycaemia in a large sample of patients with type 2 diabetes mellitus. Diabetologia 49(5):846–854PubMedCrossRefGoogle Scholar
  6. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72:248–254PubMedCrossRefGoogle Scholar
  7. Brooks CL, Gu W (2004) Dynamics in the p53-Mdm2 ubiquitination pathway. Cell cycle Georgetown 3(7):895–899Google Scholar
  8. Chehab NH, Malikzay A, Stavridi ES, Halazonetis TD (1999) Phosphorylation of Ser-20 mediates stabilization of human p53 in response to DNA damage. Proc Natl Acad Sci U S A 96(24):13777–13782PubMedCrossRefGoogle Scholar
  9. Fito M, Guxens M, Corella D, Saez G, Estruch R, de la Torre R, Frances F, Cabezas C, Lopez-Sabater Mdel C, Marrugat J, Garcia-Arellano A, Aros F, Ruiz-Gutierrez V, Ros E, Salas-Salvado J, Fiol M, Sola R, Covas MI (2007) Effect of a traditional Mediterranean diet on lipoprotein oxidation: a randomized controlled trial. Arch Intern Med 167(11):1195–1203PubMedCrossRefGoogle Scholar
  10. Forsmark-Andree P, Ernster L (1994) Evidence for a protective effect of endogenous ubiquinol against oxidative damage to mitochondrial protein and DNA during lipid peroxidation. Mol Aspects Med 15(Suppl):s73–81PubMedCrossRefGoogle Scholar
  11. Huertas JR, Battino M, Lenaz G, Mataix FJ (1991) Changes in mitochondrial and microsomal rat liver coenzyme Q9 and Q10 content induced by dietary fat and endogenous lipid peroxidation. FEBS Lett 287(1–2):89–92PubMedCrossRefGoogle Scholar
  12. Human Nutrition Information Service DoACof (1987). Washington, DCGoogle Scholar
  13. Jimenez-Gomez Y, Marin C, Peerez-Martinez P, Hartwich J, Malczewska-Malec M, Golabek I, Kiec-Wilk B, Cruz-Teno C, Rodriguez F, Gomez P, Gomez-Luna MJ, Defoort C, Gibney MJ, Perez-Jimenez F, Roche HM, Lopez-Miranda J (2010) A low-fat, high-complex carbohydrate diet supplemented with long-chain (n-3) fatty acids alters the postprandial lipoprotein profile in patients with metabolic syndrome. The Journal of Nutrition 140(9):1595–1601PubMedCrossRefGoogle Scholar
  14. Ko LJ, Prives C (1996) p53: puzzle and paradigm. Genes Dev 10(9):1054–1072PubMedCrossRefGoogle Scholar
  15. Kussie PH, Gorina S, Marechal V, Elenbaas B, Moreau J, Levine AJ, Pavletich NP (1996) Structure of the MDM2 oncoprotein bound to the p53 tumor suppressor transactivation domain. Science 274(5289):948–953PubMedCrossRefGoogle Scholar
  16. Lambeth JD, Cheng G, Arnold RS, Edens WA (2000) Novel homologs of gp91phox. Trends Biochem Sci 25(10):459–461PubMedCrossRefGoogle Scholar
  17. Li M, Brooks CL, Wu-Baer F, Chen D, Baer R, Gu W (2003) Mono- versus polyubiquitination: differential control of p53 fate by Mdm2. Science 302(5652):1972–1975PubMedCrossRefGoogle Scholar
  18. Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, Franch HA, Franklin B, Kris-Etherton P, Harris WS, Howard B, Karanja N, Lefevre M, Rudel L, Sacks F, Van Horn L, Winston M, Wylie-Rosett J (2006) Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation 114(1):82–96PubMedCrossRefGoogle Scholar
  19. Mataix J, Quiles JL, Huertas JR, Battino M, Manas M (1998) Tissue specific interactions of exercise, dietary fatty acids, and vitamin E in lipid peroxidation. Free Radic Biol Med 24(4):511–521PubMedCrossRefGoogle Scholar
  20. Monnier L, Mas E, Ginet C, Michel F, Villon L, Cristol JP, Colette C (2006) Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA 295(14):1681–1687PubMedCrossRefGoogle Scholar
  21. O’Keefe JH, Bell DS (2007) Postprandial hyperglycemia/hyperlipidemia (postprandial dysmetabolism) is a cardiovascular risk factor. Am J Cardiol 100(5):899–904PubMedCrossRefGoogle Scholar
  22. Ochoa-Herrera JJ, Huertas JR, Quiles JL, Mataix J (2001) Dietary oils high in oleic acid, but with different non-glyceride contents, have different effects on lipid profiles and peroxidation in rabbit hepatic mitochondria. J Nutr Biochem 12(6):357–364PubMedCrossRefGoogle Scholar
  23. Quiles JL, Huertas JR, Battino M, Ramirez-Tortosa MC, Cassinello M, Mataix J, Lopez-Frias M, Manas M (2002) The intake of fried virgin olive or sunflower oils differentially induces oxidative stress in rat liver microsomes. Br J Nutr 88(1):57–65PubMedCrossRefGoogle Scholar
  24. Quiles JL, Huertas JR, Manas M, Battino M, Mataix J (1999) Physical exercise affects the lipid profile of mitochondrial membranes in rats fed with virgin olive oil or sunflower oil. Br J Nutr 81(1):21–24PubMedGoogle Scholar
  25. Quiles JL, Ochoa JJ, Huertas JR, Mataix J (2004) Coenzyme Q supplementation protects from age-related DNA double-strand breaks and increases lifespan in rats fed on a PUFA-rich diet. Exp Gerontol 39(2):189–194PubMedCrossRefGoogle Scholar
  26. Ramirez-Tortosa MC, Urbano G, Lopez-Jurado M, Nestares T, Gomez MC, Mir A, Ros E, Mataix J, Gil A (1999) Extra-virgin olive oil increases the resistance of LDL to oxidation more than refined olive oil in free-living men with peripheral vascular disease. J Nutr 129(12):2177–2183PubMedGoogle Scholar
  27. Rifai N, Tracy RP, Ridker PM (1999) Clinical efficacy of an automated high-sensitivity C-reactive protein assay. Clin Chem 45(12):2136–2141PubMedGoogle Scholar
  28. Sablina AA, Budanov AV, Ilyinskaya GV, Agapova LS, Kravchenko JE, Chumakov PM (2005) The antioxidant function of the p53 tumor suppressor. Nat Med 11(12):1306–1313PubMedCrossRefGoogle Scholar
  29. Santos-Gonzalez M, Gomez Diaz C, Navas P, Villalba JM (2007) Modifications of plasma proteome in long-lived rats fed on a coenzyme Q10-supplemented diet. Exp Gerontol 42(8):798–806PubMedCrossRefGoogle Scholar
  30. Sen CKPL (1996) Antioxidant and redox regulation of gene transcription. FASEB J 10:709–720PubMedGoogle Scholar
  31. Stocker R, Bowry VW, Frei B (1991) Ubiquinol-10 protects human low density lipoprotein more efficiently against lipid peroxidation than does alpha-tocopherol. Proc Natl Acad Sci U S A 88(5):1646–1650PubMedCrossRefGoogle Scholar
  32. Stommel JM, Wahl GM (2005) A new twist in the feedback loop: stress-activated MDM2 destabilization is required for p53 activation. Cell cycle 4(3):411–417PubMedCrossRefGoogle Scholar
  33. Thomas SR, Neuzil J, Stocker R (1996) Cosupplementation with coenzyme Q prevents the prooxidant effect of alpha-tocopherol and increases the resistance of LDL to transition metal-dependent oxidation initiation. Arterioscler Thromb Vasc Biol 16(5):687–696PubMedCrossRefGoogle Scholar
  34. Turunen M, Olsson J, Dallner G (2004) Metabolism and function of coenzyme Q. Biochim Biophys Acta 1660(1–2):171–199PubMedGoogle Scholar
  35. Varela G (1980) Tablas de composición de alimentos (food composition tables). Instituto de Nutrición CSIC, MadridGoogle Scholar
  36. Weissman A, Lowenstein L, Peleg A, Thaler I, Zimmer EZ (2006) Power spectral analysis of heart rate variability during the 100-g oral glucose tolerance test in pregnant women. Diab Care 29(3):571–574CrossRefGoogle Scholar
  37. Yubero-Serrano EM, Delgado-Casado N, Delgado-Lista J, Perez-Martinez P, Tasset-Cuevas I, Santos-Gonzalez M, Caballero J, Garcia-Rios A, Marin C, Gutierrez-Mariscal FM, Fuentes F, Villalba JM, Tunez I, Perez-Jimenez F, Lopez-Miranda J (2010) Postprandial antioxidant effect of the Mediterranean diet supplemented with coenzyme Q10 in elderly men and women. Age (Dordr). doi: 10.1007/s11357-010-9199-8
  38. Zilversmit DB (1979) Atherogenesis: a postprandial phenomenon. Circulation 60(3):473–485PubMedGoogle Scholar

Copyright information

© American Aging Association 2011

Authors and Affiliations

  • Francisco M. Gutierrez-Mariscal
    • 1
  • Pablo Perez-Martinez
    • 1
  • Javier Delgado-Lista
    • 1
  • Elena M. Yubero-Serrano
    • 1
  • Antonio Camargo
    • 1
  • Nieves Delgado-Casado
    • 1
  • Cristina Cruz-Teno
    • 1
  • Monica Santos-Gonzalez
    • 4
  • Fernando Rodriguez-Cantalejo
    • 2
  • Justo P. Castaño
    • 3
  • Jose M. Villalba-Montoro
    • 4
  • Francisco Fuentes
    • 1
  • Francisco Perez-Jimenez
    • 1
  • Jose Lopez-Miranda
    • 1
    • 5
    Email author
  1. 1.Lipid and Atherosclerosis UnitIMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto Salud Carlos IIICórdobaSpain
  2. 2.Clinical Analysis ServiceReina Sofia University HospitalCórdobaSpain
  3. 3.Department of Cell Biology, Physiology and ImmunologyIMIBIC/Reina Sofia University Hospital/University of Cordoba, and CIBER Fisiopatologia Obesidad y Nutricion (CIBEROBN), Instituto Salud Carlos IIICórdobaSpain
  4. 4.Department of Cell Biology, Physiology and ImmunologyUniversity of CordobaCórdobaSpain
  5. 5.Lipid and Atherosclerosis UnitReina Sofia University HospitalCórdobaSpain

Personalised recommendations