Skip to main content

Advertisement

Log in

Potentiation of UVB-induced apoptosis by novel phytosphingosine derivative, tetraacetyl phytosphingosine in HaCaT cell and mouse skin

  • Published:
Apoptosis Aims and scope Submit manuscript

Abstract

Inappropriate apoptosis results in the epidermal hyperplasia as in psoriasis and UVB irradiation has been successfully used to treat this kind of skin disorders. Previously, we reported that the novel phytosphingosine derivative, tetraacetyl phytosphingosine (TAPS) induced apoptosis in HaCaT cells. This study examined the effect of UVB irradiation and/or TAPS on the induction of apoptosis in HaCaT. 10 mJ/cm2 of UVB irradiation or 10 μM of TAPS alone exhibited weak cytotoxicity but co-treatment of UVB and TAPS synergistically enhanced the cytotoxicity and apoptosis in HaCaT. The cells treated with UVB and TAPS showed much higher levels of cleaved caspase-3, -8, -9 and Bax than with UVB or TAPS alone, whereas Bcl-2 level was decreased by co-administration of UVB and TAPS. In hairless mice, co-treatment of UVB and TAPS synergistically increased apoptosis, as shown in the HaCaT co-treated with UVB and TAPS. Furthermore, UVB irradiation caused an increase of apoptotic cells in the epidermis and the TAPS-treated mice showed an increase of apoptotic cells in the dermis as well as in the epidermis. These results suggest that the TAPS co-treatment synergistically increases the level of UVB-induced apoptosis via caspase activation by regulating the level of pro-apoptotic Bax and anti-apoptotic Bcl-2.

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. Elder DE. Human melanocytic neoplasms and their etiologic relationship with sunlight. J Invest Dermatol 1989; 92: 297S–303S.

    CAS  PubMed  Google Scholar 

  2. Nomura T, Nakajima H, Hongyo T, et al. Induction of cancer, actinic keratosis, and specific p53 mutations by UVB light in human skin maintained in severe combined immunodeficient mice. Cancer Res 1997; 57: 2081–2084.

    CAS  PubMed  Google Scholar 

  3. Cadet J, Berger M, Douki T, et al. Effects of UV and visible radiation on DNA-final base damage. Biol Chem 1997; 378: 1275–1286.

    CAS  PubMed  Google Scholar 

  4. Ley RD. Photoreactivation in humans. Proc Natl Acad Sci USA 1993; 90: 4337.

    CAS  PubMed  Google Scholar 

  5. Matsui MS, deLeo VA. Photocarcinogenesis by ultraviolet A and B. In: Mukhtar H, ed. Boca Raton, FL: CRC Press Inc. 1995: 21–30.

    Google Scholar 

  6. Ananthaswamy HN, Pierceall WE. Molecular mechanisms of ultraviolet radiation carcinogenesis. Photochem Photobiol 1990; 52: 1119–1136.

    CAS  PubMed  Google Scholar 

  7. Staberg B, Wulf HC, Klemp P, et al. The carcinogenic effect of UVA irradiation. J Invest Dermatol 1983; 81: 517–519.

    Article  CAS  PubMed  Google Scholar 

  8. Kerscher M, Volkenandt M, Plewig G, Lehmann P. Combination phototherapy of psoriasis with calcipotriol and narrowband UVB. Lancet 1993; 342: 923.

    Article  CAS  Google Scholar 

  9. Storbeck K, Holzle E, Schurer N, et al. Narrow-band UVB (311nm) versus conventional broad-band UVB with and without dithranol in phototherapy for psoriasis. J Am Acad Dermatol 1993; 28(2 Pt 1): 227–231.

    CAS  PubMed  Google Scholar 

  10. Maceyka M, Payne SG, Milstien S, Spiegel S. Sphingosine kinase, sphingosine-1-phosphate, and apoptosis. Biochim Biophys Acta 2002; 1585: 193–201.

    CAS  PubMed  Google Scholar 

  11. Hannun YA, Luberto C. Ceramide in the eukaryotic stress response. Trends Cell Biol 2000; 10: 73–80.

    CAS  PubMed  Google Scholar 

  12. Spiegel S, Milstien S. Sphingosine-1-phosphate: Signaling inside and out. FEBS Lett 2000; 76: 55–57.

    Google Scholar 

  13. Kolesnick R, Hannun YA. Ceramide and apoptosis. Trends Biochem Sci 1999; 24: 224–225; author reply 227.

    CAS  PubMed  Google Scholar 

  14. Alessenko AV. The role of sphingomyelin cycle metabolites in transduction of signals of cell proliferation, differentiation and death. Membr Cell Biol 2000; 13: 303–320.

    CAS  PubMed  Google Scholar 

  15. Ohta H, Sweeney EA, Masamune A, et al. Induction of apoptosis by sphingosine in human leukemic HL-60 cells: A possible endogenous modulator of apoptotic DNA fragmentation occurring during phorbol ester-induced differentiation. Cancer Res 1995; 55: 691–697.

    CAS  PubMed  Google Scholar 

  16. Verheij M, Bose R, Lin XH, et al. Requirement for ceramideinitiated SAPK/JNK signalling in stress-induced apoptosis. Nature 1996; 380: 75–79.

    CAS  PubMed  Google Scholar 

  17. Zhang Y, Mattjus P, Schmid PC, et al. Involvement of the acid sphingomyelinase pathway in uva-induced apoptosis. J Biol Chem 2001; 276: 11775–11782.

    CAS  PubMed  Google Scholar 

  18. Hannun YA. Functions of ceramide in coordinating cellular responses to stress. Science 196; 274: 1855-1859.

  19. Magnoni C, Euclidi E, Benassi L, et al. Ultraviolet B radiation induces activation of neutral and acidic sphingomyelinases and ceramide generation in cultured normal human keratinocytes. Toxicol In Vitro 2002; 16: 349–355.

    Article  CAS  PubMed  Google Scholar 

  20. Cuvillier O. Sphingosine in apoptosis signaling. Biochim Biophys Acta 2002; 1585: 153–162.

    CAS  PubMed  Google Scholar 

  21. Dickson RC. Sphingolipid functions in Saccharomyces cerevisiae: Comparison to mammals. Annu Rev Biochem 1998; 67:27–48.

    CAS  PubMed  Google Scholar 

  22. Schurer NY, Plewig G, Elias PM. Stratum corneum lipid function. Dermatologica 183: 77–94, 1991.

    CAS  PubMed  Google Scholar 

  23. Jenkins GM, Richards A, Wahl T, et al. Involvement of yeast sphingolipids in the heat stress response of Saccharomyces cerevisiae. J Biol Chem 1997; 272: 32566–32572.

    CAS  PubMed  Google Scholar 

  24. Wells GB, Dickson RC, Lester RL. Heat-induced elevation of ceramide in Saccharomyces cerevisiae via de novo synthesis. J Biol Chem 1998; 273: 7235–7243.

    CAS  PubMed  Google Scholar 

  25. Lee JS, Min DS, Park C, et al. Phytosphingosine and C2-phytoceramide induce cell death and inhibit carbachol stimulated phospholipase D activation in Chinese hamster ovary cells expressing the Caenorhabditis elegans muscarinic acetylcholine receptor. FEBS Lett 2001; 499: 82–86.

    CAS  PubMed  Google Scholar 

  26. Kim HJ, Kim HJ, Kim SH, Kim TY. Tetraacetyl phytosphingosine-induced caspase activation and apoptosis occur through G2 arrest in human keratinocyte HaCaT cells. J Invest Dermatol 2003a; 121: 1135–1137.

    PubMed  Google Scholar 

  27. Kim HJ, Kim HJ, Lim SC, et al. Induction of apoptosis and expression of cell cycle regulatory proteins in response to a phytosphingosine derivative in HaCaT human keratinocyte cells. Mol Cells 2003b; 16: 331–337.

    CAS  PubMed  Google Scholar 

  28. Kim HJ, Shin W, Park CS, et al. Differential regulation of cyclooxygenase-2 expression by phytosphingosine derivatives, NAPS and TAPS, and its role in the NAPS or TAPS-mediated apoptosis. J Invest Dermatol 2003c; 121: 1126–1134.

    CAS  PubMed  Google Scholar 

  29. Wilson R, Spier RE. Biochemistry of hybridoma technology. Dev Biol Stand 1987; 66: 161–167.

    CAS  PubMed  Google Scholar 

  30. Telford WG, King LE, Fraker PJ. Rapid quantitation of apoptosis in pure and heterogeneous cell populations using flow cytometry. J Immunol Methods 1994; 172: 1–16.

    CAS  PubMed  Google Scholar 

  31. van Weelden H, De La Faille HB, Young E, van der Leun JC. A new development in UVB phototherapy of psoriasis. Br J Dermatol 1988; 119: 11–19.

    CAS  PubMed  Google Scholar 

  32. Picot E, Meunier L, Picot-Debeze MC, et al. Treatment of psoriasis with a 311-nm UVB lamp. Br J Dermatol 1992; 127: 509–512.

    CAS  PubMed  Google Scholar 

  33. Karvonen J, Kokkonen EL, Ruotsalainen E. 311 nm UVB lamps in the treatment of psoriasis with the Ingram regimen. Acta Derm Venereol 1989; 69: 82–85.

    CAS  PubMed  Google Scholar 

  34. Behrens S, Grundmann-Kollmann M, Schiener R, et al. Combination phototherapy of psoriasis with narrow-band UVB irradiation and topical tazarotene gel. J Am Acad Dermatol 2000; 42: 493–495.

    CAS  PubMed  Google Scholar 

  35. Liefer KM, Koster MI, Wang XJ, et al. Down-regulation of p63 is required for epidermal UV-B-induced apoptosis. Cancer Res 2000; 60: 4016–4020.

    CAS  PubMed  Google Scholar 

  36. Leverkus M, Yaar M, Gilchrest BA. Fas/Fas ligand interaction contributes to UV-induced apoptosis in human keratinocytes. Exp Cell Res 1997; 232: 255–262.

    CAS  PubMed  Google Scholar 

  37. Goldstein JC, Waterhouse NJ, Juin P, et al. The coordinate release of cytochrome c during apoptosis is rapid, complete and kinetically invariant. Nat Cell Biol 2000; 2: 156–162.

    CAS  PubMed  Google Scholar 

  38. Okazaki T, Bielawska A, Bell RM, Hannun YA. Role of ceramide as a lipid mediator of 1 alpha, 25-dihydroxyvitamin D3-induced HL-60 cell differentiation. J Biol Chem 1990; 265: 15823–15831.

    CAS  PubMed  Google Scholar 

  39. Spiegel S, Foster D, Kolesnick R. Signal transduction through lipid second messengers. Curr Opin Cell Biol 1996; 8: 159–167.

    CAS  PubMed  Google Scholar 

  40. Huang C, Ma W, Ding M, et al. Direct evidence for an important role of sphingomyelinase in ultraviolet-induced activation of c-Jun N-terminal kinase. J Biol Chem 1997; 272: 27753–27757.

    CAS  PubMed  Google Scholar 

  41. Sbrissa D, Yamada H, Hajra A, Bitar KN. Bombesinstimulated ceramide production and MAP kinase activation in rabbit rectosigmoid smooth muscle cells. Am J Physiol 1997; 272: G1615–1625.

    CAS  PubMed  Google Scholar 

  42. Herschman HR. Prostaglandin synthase 2. Biochim Biophys Acta 1996; 1299: 125–140.

    CAS  PubMed  Google Scholar 

  43. Buckman SY, Gresham A, Hale P, et al. COX-2 expression is induced by UVB exposure in human skin: Implications for the development of skin cancer. Carcinogenesis 1998; 19: 723–729.

    CAS  PubMed  Google Scholar 

  44. Garcia-Ruiz C, Colell A, Mari M, et al. Direct Effect of Ceramide on the Mitochondrial Electron Transport Chain Leads to Generation of Reactive Oxygen Species. J Biol Chem 1997; 272: 11369–11377.

    CAS  PubMed  Google Scholar 

  45. Quillet-Mary A, Jaffrezou JP, Mansat V, et al. Implication of Mitochondrial Hydrogen Peroxide Generation in Ceramideinduced Apoptosis. J Biol Chem 1997; 272: 21388–21395.

    CAS  PubMed  Google Scholar 

  46. Yoshimura S, Banno Y, Nakashima S, et al. Ceramide formation leads to caspase-3 activation during hypoxic PC12 cell death. J Biol Chem 1998; 273: 6921–6927.

    CAS  PubMed  Google Scholar 

  47. Kondo T, Matsuda T, Kitano T, et al. Role of c-jun expression increased by heat shock-and ceramide-activated caspase-3 in HL-60 cell apoptosis. J Biol Chem 2000; 275: 7668–7676.

    CAS  PubMed  Google Scholar 

  48. Pahan K, Sheikh FG, Khan M, et al. Sphingomyelinase and ceramide stimulate the expression of inducible nitric-oxide synthase in rat primary astrocytes. J Biol Chem 1998; 273: 2591–2600.

    CAS  PubMed  Google Scholar 

  49. Deveraux QL, Roy N, Stennicke HR, et al. IAPs block apoptotic events induced by caspase-8 and cytochrome c by directinhibition of distinct caspases. EMBO J 1998; 17: 2215–2223.

    CAS  PubMed  Google Scholar 

  50. Kluck RM, Bossy-Wetzel E, Green DR, Newmeyer DD. The release of cytochrome c from mitochondria: A primary site for Bcl-2 regulation of apoptosis. Science 1997; 275: 1132–1136.

    Article  CAS  PubMed  Google Scholar 

  51. Gross A, Jockel J, Wei MC, Korsmeyer SJ. Enforced dimerization of BAX results in its translocation, mitochondrial dysfunction and apoptosis. EMBO J 1998; 17: 3878–3885.

    CAS  PubMed  Google Scholar 

  52. Rosette C, Karin M. Ultraviolet light and osmotic stress: Activation of the JNK cascade through multiple growth factor and cytokine receptors. Science 1996; 274: 1194–1197.

    CAS  PubMed  Google Scholar 

  53. Devary Y, Gottlieb RA, Smeal T, Karin M. The mammalian ultraviolet response is triggered by activation of Src tyrosine kinases. Cell 1992; 71: 1081–1091.

    CAS  PubMed  Google Scholar 

  54. Minden A, Lin A, McMahon M, et al. Differential activation of ERK and JNK mitogen-activated protein kinases by Raf-1 and MEKK. Science 1994; 266: 1719–1723.

    CAS  PubMed  Google Scholar 

  55. Coso OA, Chiariello M, Yu JC, et al. The small GTP-inding proteins Rac1 and Cdc42 regulate the activity of the JNK/SAPK signaling pathway. Cell 1995; 81: 1137–1146.

    CAS  PubMed  Google Scholar 

  56. Smith ML, Fornace AJ Jr: p53-mediated protective responses to UV irradiation. Proc Natl Acad Sci USA 1997; 94: 12255–12257.

    CAS  PubMed  Google Scholar 

  57. Huang C, Ma W, Bowden GT, Dong Z. Ultraviolet B-induced activated protein-1 activation does not require epidermal growth factor receptor but is blocked by a dominant negative PKClambda/iota. J Biol Chem 1996; 271: 31262–31268.

    CAS  PubMed  Google Scholar 

  58. Bonni A, Brunet A, West AE, et al. Cell survival promoted by the Ras-MAPK signaling pathway by transcription-dependent and-independent mechanisms. Science 1999; 286: 1358–1362.

    CAS  PubMed  Google Scholar 

  59. Meier P, Evan G. Dying like flies. Cell 1998; 95: 295–298.

    CAS  PubMed  Google Scholar 

  60. Xia Z, Dickens M, Raingeaud J, et al. Opposing effects of ERK and JNK-p38 MAP kinases on apoptosis. Science 1995; 270: 1326–1331.

    CAS  PubMed  Google Scholar 

  61. Pena LA, Fuks Z, Kolesnick R. Stress-induced apoptosis and the sphingomyelin pathway. Biochem Pharmacol 1997; 53: 615–621.

    CAS  PubMed  Google Scholar 

  62. Park MT, Choi JA, Kim MJ, et al. Suppression of extracellular signal-related kinase and activation of p38 MAPK are two critical events leading to caspase-8-and mitochondria-mediated cell death in phytosphingosine-treated human cancer cells. J Biol Chem 2003; 278: 50624–50634

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T.-Y. Kim.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, H.J., Kang, SY., Kim, S.J. et al. Potentiation of UVB-induced apoptosis by novel phytosphingosine derivative, tetraacetyl phytosphingosine in HaCaT cell and mouse skin. Apoptosis 9, 449–456 (2004). https://doi.org/10.1023/B:APPT.0000031451.62428.f0

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:APPT.0000031451.62428.f0

Navigation