Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Protection of normal human reconstructed epidermis from UV by catalase overexpression

Cancer Gene Therapy volume 14, pages 174–186 (2007)Cite this article

Abstract

Reactive oxygen species (ROS) generated by ultraviolet (UV) irradiation are counterbalanced by endogenous antioxidant systems. To test the hypothesis of a novel photoprotective approach, we irradiated epidermis reconstructed with normal human keratinocytes overexpressing sustainably lentivirus-mediated catalase (CAT), copper/zinc superoxide dismutase (CuZnSOD) or manganese superoxide dismutase (MnSOD) enzymes. We found that following UVB irradiation there was a marked decrease in sunburn cell formation, caspase-3 activation and p53 accumulation in human reconstructed epidermis overexpressing CAT. Moreover, UVA-induced hypertrophy and DNA oxidation (8-oxodeoxyguanosine) were decreased by CAT overexpression. These effects were not achieved by overexpression of CuZnSOD or MnSOD. In conclusion, vector-mediated CAT overexpression could be a promising photoprotective tool against deleterious effects of UV irradiation such skin cancer especially in monogenic/polygenic photosensitive disorders characterized by ROS accumulation.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7

Similar content being viewed by others

Abbreviations

CAT:

catalase

CPD:

cyclobutane pyrimidine dimer

CuZnSOD:

copper/zinc superoxide dismutase

E:

epidermis

MnSOD:

manganese superoxide dismutase

NT:

non-transduced

nIr:

non-irradiated

ODC:

ornithine decarboxylase

8-oxodG:

8-oxodeoxyguanosine

RE:

reconstructed epidermis

SBC:

sunburn cell

SVHK:

SV40-transformed human keratinocytes

References

  1. de Gruijl FR, van Kranen HJ, Mullenders LH . UV-induced DNA damage, repair, mutations and oncogenic pathways in skin cancer. J Photochem Photobiol B Biol 2001; 63: 19–27.

    Article  CAS  Google Scholar 

  2. Boukamp P . Non-melanoma skin cancer: what drives tumor development and progression? Carcinogenesis 2005; 26: 1657–1667 (Review).

    Article  CAS  Google Scholar 

  3. Djavaheri-Mergny M, Mergny JL, Bertrand F, Santus R, Maziere C, Dubertret L et al. Ultraviolet-A induces activation of AP-1 in cultured human keratinocytes. FEBS Lett 1996; 384: 92–96.

    Article  CAS  Google Scholar 

  4. Tyrrell R . Redox regulation and oxidant activation of heme oxygenase-1. Free Radic Res 1999; 31: 335–340.

    Article  CAS  Google Scholar 

  5. Fuchs J, Packer L . Ultraviolet irradiation and the skin antioxidant system. Photodermatol Photoimmunol Photomed 1990; 7: 90–92.

    CAS  PubMed  Google Scholar 

  6. Danno K, Horio T . Sunburn cell: factors involved in its formation. Photochem Photobiol 1987; 45: 683–690.

    Article  CAS  Google Scholar 

  7. Bayerl C, Taak S, Moll I, Jung EG . Characterization of sunburn cells after exposure to ultraviolet light. Photodermatol Photoimmunol Photomed 1995; 11: 149–154.

    Article  CAS  Google Scholar 

  8. Schwarz A, Bhardwaj R, Aragane Y, Mahnke K, Riemann H, Metze D et al. Ultraviolet-B-induced apoptosis of keratinocytes: evidence for partial involvement of tumor necrosis factor-alpha in the formation in the formation of sunburn cells. J Invest Dermatol 1995; 104: 922–927.

    Article  CAS  Google Scholar 

  9. Aragane Y, Kulms D, Metze D, Wilkes G, Pöppelmann B, Luger TA et al. Ultraviolet light induces apoptosis via direct activation of CD95 (Fas/APO-1) independently of its ligand CD95L. J Cell Biol 1998; 140: 171–182.

    Article  CAS  Google Scholar 

  10. Masaki H, Atsumi T, Sakurai H . Detection of hydrogen peroxide and hydroxyl radicals in murine skin fibroblasts under UVB irradiation. Biochem Biophys Res Commun 1995; 17: 474–479.

    Article  Google Scholar 

  11. Peus D, Vasa RA, Beyerle A, Meves A, Krautmacher C, Pittelkow MR . H2O2 is an important mediator of UVB-induced EGF-receptor phosphorylation in cultured keratinocytes. J Invest Dermatol 1999; 112: 751–756.

    Article  CAS  Google Scholar 

  12. Murphy G, Young AR, Wulf HC, Kulms D, Schwarz T . The molecular determinations of sunburn cell formation. Exp Dermatol 2001; 10: 155–160.

    Article  CAS  Google Scholar 

  13. Matés JM . Effects of antioxidant enzymes in the molecular control of reactive oxygen species toxicology. Toxicol 2000; 153: 83–104.

    Article  Google Scholar 

  14. Vile GF, Tyrrell RM . Oxidative stress resulting from ultraviolet A irradiation of human skin fibroblasts leads to a heme oxygenase-dependent increase in ferritin. J Biol Chem 1993; 268: 14678–14681.

    CAS  PubMed  Google Scholar 

  15. Punnonen K, Puntala A, Ahtupa M . Effects of ultaviolet A and B irradiation on lipid peroxidation and activity of the antioxidant enzymes in keratinocytes in culture. Photodermatol Photoimmunol Photomed 1991; 8: 3–6.

    CAS  PubMed  Google Scholar 

  16. Shindo Y, Witt E, Han D, Tzeng B, Aziz T, Nguyen L et al. Recovery of antioxidants and reduction in lipid hydroperoxides in murine epidermis and dermis after acute ultraviolet radiation exposure. Photodermatol Photoimmunol Photomed 1994; 10: 183–191.

    CAS  PubMed  Google Scholar 

  17. Zhang X, Rosenstein BS, Wang Y, Lebwohl M, Wei H . Identification of possible reactive oxygen species involved in ultraviolet radiation-induced oxidative DNA damage. Free Radic Biol Med 1997; 23: 980–985.

    Article  CAS  Google Scholar 

  18. Pelle E, Hung X, Mammone T, Marenus K, Maes D, Frenkek K . Ultraviolet-B-induced oxidative DNA base damage in primary normal human epidermal keratinocytes and inhibition by a hydroxyl radical scavenger. J Invest Dermatol 2003; 121: 177–183.

    Article  CAS  Google Scholar 

  19. Maalouf S, El-Sabban M, Drawiche N, Gali-Muhtasib H . Protective effect of vitamin E on ultraviolet B light-induced damage in keratinocytes. Mol Carcinogen 2000; 34: 121–130.

    Article  Google Scholar 

  20. Morley N, Curnow A, Salter L, Campbell S, Gould D . N-acetyl-L-cysteine prevents DNA damage induced by UVA, UVB and visible radiation in human fibroblasts. J Photochem Photobiol B Biol 2003; 72: 55–60.

    Article  CAS  Google Scholar 

  21. Cario-Andre M, Briganti S, Picardo M, Nikaido O, Gall Y, Ginestar J et al. Epidermal reconstructs: a new tool to study topical and systemic photoprotective molecules. J Photochem Photobiol B Biol 2002; 68: 79–87.

    Article  CAS  Google Scholar 

  22. Rezvani HR, Mazurier F, Cario-André M, Pain C, Ged C, Taïeb A et al. Protective effects of catalase overexpression on UVB-induced apoptosis in normal human keratinocytes. J Biol Chem 281: 17999–18007.

    Article  CAS  Google Scholar 

  23. Sander CS, Hamm F, Elsner P, Thiele JJ . Oxidative stress in malignant melanoma and non-melanoma skin cancer. Br J Dermatol 2003; 148: 913–922.

    Article  CAS  Google Scholar 

  24. Prunieras M, Régnier M, Schlotterer M . Nouveau procédé de culture des cellules épidermiques humaines sur derme homologue ou hétérologue: préparation de greffons recombines. Ann Chir Plast 1979; 24: 357–362.

    CAS  PubMed  Google Scholar 

  25. Cudre-Mauroux C, Occhiodoro T, Konig S, Salmon P, Bernheim L, Trono D . Lentivector-mediated transfer of Bmi-1 and telomerase in muscle satellite cells yields a Duchenne myoblast cell line with long-term genotypic and phenotypic stability. Hum Gene Ther 2003; 14: 1525–1533.

    Article  CAS  Google Scholar 

  26. Géronimi F, Richard E, Redonnet-Vernhet I, Lamrissi-Garcia I, Lalanne M, Ged C et al. Highly efficient lentiviral gene transfer in CD34+ and CD34+/CD38−/lin− cells from mobilized peripheral blood after cytokine prestimulation. Stem Cells 2003; 21: 472–480.

    Article  Google Scholar 

  27. Chen M, Li W, Fan J, Kasahara N, Woodley D . An efficient gene transduction system for studying gene function in primary human dermal fibroblasts and epidermal keratinocytes. Clin Exp Dermatol 2003; 28: 193–199.

    Article  CAS  Google Scholar 

  28. Serrano F, Del Rio M, Larcher F, Garcia M, Munoz E, Escamez MJ et al. A comparison of targeting performance of oncoretroviral versus lentiviral vectors on human keratinocytes. Hum Gene Ther 2003; 14: 1579–1585.

    Article  CAS  Google Scholar 

  29. Ghazizadeh S, Katz AB, Harrington R, Taichman LB . Lentivirus-mediated gene transfer to human epidermis. J Investig Dermatol Symp Proc 2004; 9: 269–275.

    Article  CAS  Google Scholar 

  30. Amstad P, Peskin A, Shah G, Mirault ME, Moret R, Zbinden I et al. The balance between Cu,Zn-superoxide dismutase and catalase affects the sensitivity of mouse epidermal cells to oxidative stress. Biochemistry 1991; 30: 9305–9313.

    Article  CAS  Google Scholar 

  31. Takahashi H, Hashimoto Y, Aoki N, Kinouchi M, Ishida-Yamamoto A, Iizuka H . Copper, zinc-superoxide dismutase protects from ultraviolet B-induced apoptosis of SV40-transformed human keratinocytes: the protection is associated with the increased levels of antioxidant enzymes. J Dermatol Sci 2000; 23: 12–21.

    Article  CAS  Google Scholar 

  32. Sasaki H, Akamatsu H, Horio T . Effects of a single exposure to UVB radiation on the activities and protein levels of copper–zinc and manganese superoxide dismutase in cultured human keratinocytes. Photochem Photobiol 1997; 65: 707–713.

    Article  CAS  Google Scholar 

  33. Hurwitz SA, Spadau DF . Quantitative analysis of UVB-induced apoptosis in human epidermis. Exp Dermatol 2000; 9: 185–191.

    Article  CAS  Google Scholar 

  34. Bedner E, Smolewski P, Amstad P, Darzynkiewicz Z . Activation of caspases measured in situ by binding of fluorochrome-labeled inhibitors of caspases (FLICA): correlation with DNA fragmentation. Exp Cell Res 2000; 259: 308–313.

    Article  CAS  Google Scholar 

  35. Zuliani T, Denis V, Noblesse E, Schnebert S, André P, Dumas M et al. Hydrogen peroxide-induced cell death in normal human keratinocytes is differentiation dependent. Free Radic Biol Med 2005; 38: 307–316.

    Article  CAS  Google Scholar 

  36. Harris CC . p53: at the crossroads of molecular carcinogenesis and risk assessment. Science 1993; 262: 1980–1981.

    Article  CAS  Google Scholar 

  37. Shieh SY, Ikeda M, Taya Y, Prives C . DNA damage-induced phosphorylation of p53 alleviates inhibition by MDM2. Cell 1997; 91: 325–334.

    Article  CAS  Google Scholar 

  38. Achanta G, Huang P . Role of p53 in sensing oxidative DNA damage in response to reactive oxygen species-generating agents. Cancer Res 2004; 64: 6233–6239.

    Article  CAS  Google Scholar 

  39. Giaccia AJ, Kastan MB . The complexity of p53 modulation: emerging patterns from divergent signals. Genes Dev 1998; 12: 2973–2983.

    Article  CAS  Google Scholar 

  40. Ko LJ, Prives C . p53: puzzle and paradigm. Genes Dev 1996; 10: 1054–1072.

    Article  CAS  Google Scholar 

  41. Levine AJ . p53, the cellular gatekeeper for growth and division. Cell 1997; 88: 323–331.

    Article  CAS  Google Scholar 

  42. Steegenga WT, vandereb AJ, Jochemsen AG . How phosphorylation regulates the activity of p53. J Mol Biol 1996; 263: 103–113.

    Article  CAS  Google Scholar 

  43. Mitchell DL, Jen J, Cleaver JE . Relative induction of cyclobutane dimers and cytosine photohydrates in DNA irradiated in vitro and in vivo with ultraviolet-C and ultraviolet-B light. Photochem Photobiol 1991; 54: 741.

    Article  CAS  Google Scholar 

  44. Doetsch PW, Zasatawny TH, Martin AM, Dizdaroglu M . Monomeric base damage products from adenine, guanine, and thymine induced by exposure of DNA to ultraviolet radiation. Biochemistry 1995; 34: 737.

    Article  CAS  Google Scholar 

  45. Cadet J, Anselmino C, Douki T, Voituriez L . Photochemistry of nucleic acids in cells. J Photochem Photobiol B Biol 1992; 15: 277.

    Article  CAS  Google Scholar 

  46. Ravanat JL, Douki T, Cadet J . Direct and indirect effects of UV radiation on DNA and its components. J Photochem Photobiol B Biol 2001; 63: 88–102 (Review).

    Article  CAS  Google Scholar 

  47. Kulms D, Zeise E, Poppelmann B, Schwarz T . DNA damage, death receptor activation and reactive oxygen species contribute to ultraviolet radiation-induced apoptosis in an essential and independent way. Oncogene 2002; 21: 5844–5851.

    Article  CAS  Google Scholar 

  48. Xanthoudakis S, Curran T . Identification and characterization of Ref-1, a nuclear protein that facilitates AP-1 DNA-binding activity. EMBO J 1992; 11: 653–665.

    Article  CAS  Google Scholar 

  49. Jayaraman L, Murthy KG, Zhu C, Curran T, Xanthoudakis S, Prives C . Identification of redox/repair protein Ref-1 as a potent activator of p53. Genes Dev 1997; 11: 558–570.

    Article  CAS  Google Scholar 

  50. Garmyn M, Degreef H . Suppression of UVB-induced c-fos and c-jun expression in human keratinocytes by N-acetylcysteine. J Photochem Photobiol B Biol 1997; 37: 125–130.

    Article  CAS  Google Scholar 

  51. Brenneisen P, Wenk J, Klotz LO, Wlaschek M, Briviba K, Krieg T et al. Central role of ferrous/ferric iron in the ultraviolet B irradiation-mediated signaling pathway leading to increased interstitial collagenase (matrix-degrading metalloprotease (MMP)-1) and stromelysin-1 (MMP-3) mRNA levels in cultured human dermal fibroblasts. J Biol Chem 1998; 273: 5279–5287.

    Article  CAS  Google Scholar 

  52. Wang H, Kochevar IE . Involvement of UVB-induced reactive oxygen species in TGF-beta biosynthesis and activation in keratinocytes. Free Radic Biol Med 2005; 38: 890–897.

    Article  CAS  Google Scholar 

  53. Lowe N, Koo L, Breeding J . Ultraviolet light induces human epidermal ornithine decarboxylase activity. Br J Dermatol 1980; 103: 18.

    Google Scholar 

  54. Berton T, Mitchell DL, Fischer SM, Locniskar MF . Epidermal proliferation but not the quantity of DNA photodamage is correlated with UV-induced mouse skin carcinogenesis. J Invest Dermatol 1997; 109: 340–347.

    Article  CAS  Google Scholar 

  55. Nakamura Y, Murakami A, Ohto Y, Torikai K, Tanaka T, Ohigashi H . Suppression of tumor promoter-induced oxidative stress and inflammatory responses in mouse skin by a superoxide generation inhibitor l′-acetoxychavicol acetate. Cancer Res 1998; 58: 4832–4839.

    CAS  PubMed  Google Scholar 

  56. Ishizaki C, Oguro T, Yoshida T, Wen CQ, Sueki H, Iijima M . Enhancing effect of ultraviolet A on ornithine decarboxylase induction and dermatitis evoked by 12-o-tetradecanoylphorbol-13-acetate and its inhibition by curumin in mouse skin. Dermatology 1996; 193: 311–317.

    Article  CAS  Google Scholar 

  57. Schieke SM, Ruwiedel K, Gers-Barlag H, Grether-Beck S, Krutmann J . Molecular crosstalk of the ultraviolet a and ultraviolet B signaling responses at the level of mitogen-activated protein kinases. J Invest Dermatol 2005; 124: 857–859.

    Article  CAS  Google Scholar 

  58. Adachi M, Gazel A, Pintucci G, Shuck A, Shifteh S, Ginsburg D et al. Specificity in stress response: epidermal keratinocytes exhibit specialized UV-responsive signal transduction pathway. DNA Cell Biol 2003; 22: 665–677.

    Article  CAS  Google Scholar 

  59. Bode AM, Dong Z . Mitogen-activated protein kinase activation in UV-induced signal transduction. Sci STKE 2003; 2003: RE2 (Review).

    PubMed  Google Scholar 

  60. Casoli V, Cario-Andre M, Costet P, Pain C, Taieb A . Comparison of long-term survival of pigmented epidermal reconstructs cultured in vitro vs xenografted on nude mice. Pigment Cell Res 2004; 17: 87–92.

    Article  Google Scholar 

  61. Sander CS, Chang H, Hamm F, Elsner P, Thiele JJ . Role of oxidative stress and the antioxidant network in cutaneous carcinogenesis. Int J Dermatol 2004; 43: 326–335 (Review).

    Article  CAS  Google Scholar 

  62. Kobayashi T, Matsumoto M, Iizuka H, Suzuki K, Taniguchi N . Superoxide dismutase in psoriasis, squamous cell carcinoma and basal cell epithelioma: an immunohistochemical study. Br J Dermatol 1991; 124: 555–559.

    Article  CAS  Google Scholar 

  63. Rabilloud T, Asselineau D, Miquel C, Calvayrac R, Darmon M, Vuillaume M . Deficiency in catalase activity correlates with the appearance of tumor phenotype in human keratinocytes. Int J Cancer 1990; 45: 952–956.

    Article  CAS  Google Scholar 

  64. F S, Afaq F, Mukhtar H . Photochemoprevention of skin cancer by botanical agents. Photodermatol Photoimmunol Photomed 2003; 19: 56–72 (Review).

    Article  Google Scholar 

  65. Vuillaume M, Calvayrac R, Best-Belpomme M, Tarroux P, Hubert M, Decroix Y et al. Deficiency in the catalase activity of xeroderma pigmentosum cell and simian virus 4-transformed human cell extracts. Cancer Res 1986; 46: 538–544.

    CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank M Longy (Institut Bergonié, France) for providing anti-p53 antibody.

Author information

Authors and Affiliations

  1. Inserm E 0217, University Victor Segalen Bordeaux 2, Bordeaux, France

    H R Rezvani, M Cario-André, C Pain, C Ged, H deVerneuil & A Taïeb

  2. Department of Dermatology, CHU Bordeaux, Hôpital St André, Bordeaux, France

    A Taïeb

Authors
  1. H R Rezvani
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M Cario-André
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C Pain
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C Ged
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. H deVerneuil
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A Taïeb
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to A Taïeb.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Rezvani, H., Cario-André, M., Pain, C. et al. Protection of normal human reconstructed epidermis from UV by catalase overexpression. Cancer Gene Ther 14, 174–186 (2007). https://doi.org/10.1038/sj.cgt.7701000

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.cgt.7701000

Keywords

This article is cited by

Search

Advanced search

Quick links