Skip to main content
Log in

Betacarotene supplementation protects from photoaging-associated mitochondrial DNA mutation

  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

Mutations of mitochondrial DNA accumulate during normal aging and can be detected at elevated levels in skin prematurely aged by chronic exposure to ultraviolet (UV) light (photoaging). In normal human fibroblasts, we have previously demonstrated that mtDNA deletions are induced by repetitive exposure to sublethal doses of UVA radiation mediated through singlet oxygen. Betacarotene is a known quencher of ROS and singlet oxygen in particular, and it is widely applied in photoprotective compounds. Therefore we investigated whether in our in vitro system, betacarotene is capable of protecting from the induction of photoaging-associated mtDNA deletions. All-E (trans) betacarotene was tested at doses from 0.25 to 3.0 μM for uptake into cells as well as its protective capacity. Assessment of cellular uptake of all-E betacarotene measured by HPLC revealed a dose dependent increase of intracellular concentrations, as well as an increase in oxidative metabolites. UVA-exposure led to a decrease of all-E-betacarotene, its Z-isomers and oxidative metabolites. Assessment of mtDNA deletions by PCR revealed reduced levels of mtDNA mutagenesis in cells coincubated with betacarotene at concentrations of 0.5 μM and higher. Taken together, these results indicate that betacarotene (i) is taken up into the cell in a dose dependent manner, (ii) interacts with UVA radiation in the cell and (iii) shows protective properties from the induction of a photoaging-associated mtDNA mutation.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. P. F. Chinnery, D. C. Samuels, J. Elson and D. M. Turnbull, Accumulation of mitochondrial DNA mutations in ageing, cancer, and mitochondrial disease: is there a common mechanism?, Lancet, 2002, 360, 1323–1325.

    Article  CAS  Google Scholar 

  2. M. Berneburg, H. Plettenberg and J. Krutmann, Photoaging of human skin, Photodermatol. Photoimmunol. Photomed., 2000, 16, 239–444.

    Article  CAS  Google Scholar 

  3. D. C. Wallace, Mitochondrial genetics: a paradigm for aging and degenerative diseases?, Science, 1992, 256, 628–632.

    Article  CAS  Google Scholar 

  4. G. J. Fisher, Z. Q. Wang, S. C. Datta, J. Varani, S. Kang and J. J. Voorhees, Pathophysiology of premature skin aging induced by ultraviolet light [see comments], N. Engl. J. Med., 1997, 337, 1419–1428.

    Article  CAS  Google Scholar 

  5. G. J. Fisher, H. S. Talwar, J. Lin, P. Lin, F. McPhillips, Z. Wang, X. Li, Y. Wan, S. Kang and J. J. Voorhees, Retinoic acid inhibits induction of c-Jun protein by ultraviolet radiation that occurs subsequent to activation of mitogen-activated protein kinase pathways in human skin in vivo, J. Clin. Invest., 1998, 101, 1432–1440.

    Article  CAS  Google Scholar 

  6. R. G. Gilchrest, Photoaging, in Clinical Photomedicine, New York, 1993, 95–111.

    Google Scholar 

  7. C. E. Griffiths, The role of retinoids in the prevention and repair of aged and photoaged skin, Clin. Exp. Dermatol., 2001, 26, 613–618.

    Article  CAS  Google Scholar 

  8. J. H. Yang, H. C. Lee, K. J. Lin and Y. H. Wei, A specific 4977-bp deletion of mitochondrial DNA in human ageing skin, Arch. Dermatol. Res., 1994, 286, 386–390.

    Article  CAS  Google Scholar 

  9. M. A. Birch-Machin, M. Tindall, R. Turner, F. Haldane and J. L. Rees, Mitochondrial DNA deletions in human skin reflect photo- rather than chronologic aging, J. Invest. Dermatol., 1998, 110, 149–152.

    Article  CAS  Google Scholar 

  10. M. Berneburg, N. Gattermann, H. Stege, M. Grewe, K. Vogelsang, T. Ruzicka and J. Krutmann, Chronically ultraviolet-exposed human skin shows a higher mutation frequency of mitochondrial DNA as compared to unexposed skin and the hematopoietic system, Photochem. Photobiol., 1997, 66, 271–275.

    Article  CAS  Google Scholar 

  11. A. J. Ray, R. Turner, O. Nikaido, J. L. Rees, M. A. Birch-Machin, The spectrum of mitochondrial DNA deletions is a ubiquitous marker of ultraviolet radiation exposure in human skin, J. Invest. Dermatol., 2000, 115, 674–679.

    Article  CAS  Google Scholar 

  12. M. Berneburg, S. Grether-Beck, V. Kürten, T. Ruzicka, K. Briviba, H. Sies and J. Krutmann, Singlet Oxygen Mediates the UVA-induced Generation of the Photoaging-associated Mitochondrial Common Deletion, J. Biol. Chem., 1999, 274, 15345–15349.

    Article  CAS  Google Scholar 

  13. N. I. Krinsky, The antioxidant and biological properties of the carotenoids, Ann. N. Y. Acad. Sci., 1998, 854, 443–447.

    Article  CAS  Google Scholar 

  14. P. Palozza and N. I. Krinsky, Antioxidant effects of carotenoids in vivo and in vitro: an overview, Methods Enzymol., 1992, 213, 403–420.

    Article  CAS  Google Scholar 

  15. H. P. M. Gollnick, W. Hopfenmueller, C. Hemmes, S. C. Chun, C. Schmid, K. Kundermeier and H. K. Biesalski, Systemic beta carotene plus topical UV sunscreen are an optimal protection against harmful effects of natural UV sunlight, Results of the Berlin–Eilath study, Eur. J. Dermatol., 1996, 6, 200–205.

    Google Scholar 

  16. M. M. Mathews-Roth, Carotenoids in erythropoietic protoporphyria and other photosensitivity diseases, Ann. N. Y. Acad. Sci., 1993, 691, 127–138.

    Article  CAS  Google Scholar 

  17. M. M. Mathews-Roth, Treatment of the cutaneous porphyrias, Clin. Dermatol., 1998, 16, 295–298.

    Article  CAS  Google Scholar 

  18. M. M. Mathews-Roth, Erythropoietic protoporphyria: treatment with antioxidants and potential cure with gene therapy, Methods Enzymol., 2000, 319, 479–484.

    Article  CAS  Google Scholar 

  19. M. C. Trekli, G. Riss, R. Goralczyk and R. M. Tyrrell, Beta carotene suppresses UVA induced HO-1 gene expression in cultured FEK4, Free Radicals Biol. Med., 2003, 34, 456–464.

    Article  CAS  Google Scholar 

  20. N. Gattermann, M. Berneburg, J. Heinisch, C. Aul and W. Schneider, Detection of the ageing-associated 5-Kb common deletion of mitochondrial DNA in blood and bone marrow of hematologically normal adults. Absence of the deletion in clonal bone marrow disorders, Leukemia, 1995, 9, 1704–1710.

    CAS  PubMed  Google Scholar 

  21. H. P. Henninger, R. Hoffmann, M. Grewe, A. Schulze-Specking and K. Decker, Purification and quantitative analysis of nucleic acids by anion-exchange-high-performance liquid chromatography, Biol. Chem. Hoppe-Seyler, 1993, 374, 625–629.

    Article  CAS  Google Scholar 

  22. S. Anderson, A. T. Bankier, B. G. Barrell, M. H. de Bruijn, A. R. Coulson, J. Drouin, I. C. Eperon, D. P. Nierlich, B. A. Roe, F. Sanger, P. H. Schreier, A. J. Smith, R. Staden and I. G. Young, Sequence and organization of the human mitochondrial genome, Nature, 1981, 290, 457–465.

    Article  CAS  Google Scholar 

  23. P. F. Conn, W. Schalch and T. G. Truscott, The singlet oxygen and carotenoid interaction, J. Photochem. Photobiol. B., 1991, 11, 41–47.

    Article  CAS  Google Scholar 

  24. C. Kiefer, S. Hessel, J. M. Lampert, K. Vogt, M. O. Lederer, D. E. Breithaupt, J. von Lintig, Identification and characterization of a mammalian enzyme catalyzing the asymmetric oxidative cleavage of provitamin A, J. Biol. Chem., 2001, 276, 14110–14116.

    Article  CAS  Google Scholar 

  25. X. D. Wang, R. M. Russell, C. Liu, F. Stickel, D. E. Smith and N. I. Krinsky, Beta-oxidation in rabbit liver in vitro and in the perfused ferret liver contributes to retinoic acid biosynthesis from beta-apocarotenoic acids, J. Biol. Chem., 1996, 271, 26490–26498.

    Article  CAS  Google Scholar 

  26. T. A. Kennedy and D. C. Liebler, Peroxyl radical oxidation of beta-carotene: Formation of beta-carotene epoxides, Chem. Res. Toxicol., 1991, 4, 472–479.

    Article  Google Scholar 

  27. T. A. Kennedy and D. C. Liebler, Peroxyl radical scavening by beta-carotene in lipid bilayers. Effect of oxygen partial pressure, J. Biol. Chem., 1992, 268, 4658–4663.

    Article  Google Scholar 

  28. A. B. Barua, Intestinal absorption of epoxy-beta-carotenes by humans, Biochem. J., 1999, 339, 359–662.

    Article  CAS  Google Scholar 

  29. P. K. Duitsman, A. B. Barua, B. Becker and J. A. Olson, Effects of epoxycarotenoids, beta-carotene, and retinoic acid on the diferentiation and viability of the leukemia cell line NB4 in vitro, Int. J. Vitam. Nutr. Res., 1999, 69, 303–308.

    Article  CAS  Google Scholar 

  30. A. A. Woodall, S. W. Lee, R. J. Weesie, M. J. Jackson and G. Britton, Oxidation of carotenoids by free radicals: relationship between structure and reactivity, Biochim. Biophys. Acta, 1997, 1336, 33–42.

    Article  CAS  Google Scholar 

  31. S. Alaluf, U. Heinrich, W. Stahl, H. Tronnier and S. Wiseman, Dietary carotenoids contribute to normal human skin color and UV photosensitivity, J. Nutr., 2002, 132, 399–403.

    Article  CAS  Google Scholar 

  32. J. H. Weisburger, Lycopene and Tomato Products in Health Promotion, Exp. Biol. Med., 2002, 227, 924–927.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Jean Krutmann.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Eicker, J., Kürten, V., Wild, S. et al. Betacarotene supplementation protects from photoaging-associated mitochondrial DNA mutation. Photochem Photobiol Sci 2, 655–659 (2003). https://doi.org/10.1039/b300808h

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/b300808h

Navigation