동의생리병리학회지 (Journal of Physiology & Pathology in Korean Medicine)

  • 제26권6호
  • /
  • Pages.922-928
  • /
  • 2012
  • /
  • 1738-7698(pISSN)
  • /
  • 2288-2529(eISSN)
대한동의생리학회·한의병리학회 ( The Physiological Society of Korean Medicine and The Society of Pathology in Korean Medicine)
권호 표지

Sulforaphane Inhibits Ultraviolet B-induced Matrix Metalloproteinase Expression in Human Dermal Fibroblasts

  • Lee, Sam Youn (Department of Thoracic and Cardiovascular Surgery, College of Medicine, Wonkwang University) ;
  • Moon, Sun Rock (Department of Radiation Oncology, College of Medicine, Wonkwang University)
  • 투고 : 2012.11.22
  • 심사 : 2012.12.20
  • 발행 : 2012.12.25
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

Sulforaphane [1-isothiocyanato-4-(methylsulfinyl)-butane] is one of the most abundant isothiocyanates in some cruciferous vegetables, especially broccoli. Sulforaphaene has been shown to exhibit many pharmacological activities, including anti-oxidant, anti-inflammatory and anti-microbial activities. However, the anti-skin photoaging effects of sulforaphane have not yet been reported. In the present study, we investigated the inhibitory effects of sulforaphane on MMP-1 and -3 expressions of the human dermal fibroblasts via various in vitro experiments and elucidated the pathways of inhibition. Western blot analysis and real-time PCR revealed sulfiraphane inhibited UVB-induced MMP-1 and -3 expressions in a dose-dependent manner. UVB strongly activated nuclear factor-${\kappa}B$ (NF-${\kappa}B$) activity, which was determined by NF-${\kappa}B$ DNA binding activity. UVB-induced NF-${\kappa}B$ activation and MMP expression were completely blocked by sulforphane. These findings suggest that sulforaphane could prevent UVB-induced MMPs expressions through inhibition of NF-${\kappa}B$ activation.

키워드

과제정보

연구 과제 주관 기관 : Wonkwang University

참고문헌

  1. Ho, J.N., Lee, Y.H., Park, J.S., Jun, W.J., Kim, H.K., Hong, B.S., Shin, D.H., Cho, H.Y. Protective effects of aucubin isolated from Eucommia ulmoides against UVB-induced oxidative stress in human skin fibroblasts. Biol Pharm Bull 28: 1244-1248, 2005. https://doi.org/10.1248/bpb.28.1244
  2. Scharffetter-Kochanek, K., Brenneisen, P., Wenk, J., Herrmann, G., Ma, W., Kuhr, L., Meewes, C., Wlaschek, M. Photoaging of the skin from phenotype to mechanisms. Exp Gerontol, 35: 307-316, 2000. https://doi.org/10.1016/S0531-5565(00)00098-X
  3. Ogata, Y., Enghild, J.J., Nagase, H. Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9. J Biol Chem, 267: 3581-3584, 1992.
  4. Knauper, V., Lopez-Otin, C., Smith, B., Knight, G., Murphy, G. Biochemical characterization of human collagenase-3. J Biol Chem, 271: 1544-1550, 1996. https://doi.org/10.1074/jbc.271.3.1544
  5. Jackson, C., Nguyen, M., Arkell, J., Sambrook, P. Selective matrix metalloproteinase (MMP) inhibition in rheumatoid arthritis-targetting gelatinase A activation. Inflamm Res, 50: 183-186, 2001. https://doi.org/10.1007/s000110050743
  6. Brenneisen, P., Sies, H., Scharffetter-Kochanek, K. Ultraviolet-B irradiation and matrix metalloproteinases: from induction via signaling to initial events. Ann N Y Acad Sci, 973: 31-43, 2002. https://doi.org/10.1111/j.1749-6632.2002.tb04602.x
  7. Brenneisen, P., Oh, J., Wlaschek, M., Wenk, J., Briviba, K., Hommel, C., Herrmann, G., Sies, H., Scharffetter-Kochanek, K. Ultraviolet B wavelength dependence for the regulation of two major matrix-metalloproteinases and their inhibitor TIMP-1 in human dermal fibroblasts. Photochem Photobiol, 64: 877-885, 1996. https://doi.org/10.1111/j.1751-1097.1996.tb01851.x
  8. Brenneisen, P., Wenk, J., Wlaschek, M., Krieg, T., Scharffetter-Kochanek, K. Activation of p70 ribosomal protein S6 kinase is an essential step in the DNA damage-dependent signaling pathway responsible for the ultraviolet B-mediated increase in interstitial collagenase (MMP-1) and stromelysin-1 (MMP-3) protein levels in human dermal fibroblasts. J Biol Chem, 275: 4336-4344, 2000. https://doi.org/10.1074/jbc.275.6.4336
  9. Wenk, J., Schuller, J., Hinrichs, C., Syrovets, T., Azoitei, N., Podda, M., Wlaschek, M., Brenneisen, P., Schneider, L.A., Sabiwalsky, A., Peters, T., Sulyok, S., Dissemond, J., Schauen, M., Krieg, T., Wirth, T., Simmet, T., Scharffetter-Kochanek, K. Overexpression of phospholipid-hydroperoxide glutathione peroxidase in human dermal fibroblasts abrogates UVA irradiation-induced expression of interstitial collagenase/matrix metalloproteinase-1 by suppression of phosphatidylcholine hydroperoxide-mediated NFkappaB activation and interleukin-6 release. J Biol Chem, 279: 45634-45642, 2004. https://doi.org/10.1074/jbc.M408893200
  10. Rittie, L., Fisher, G.J. UV-light-induced signal cascades and skin aging. Ageing Res Rev, 1: 705-720, 2002. https://doi.org/10.1016/S1568-1637(02)00024-7
  11. Moon, H.J., Lee, S.R., Shim, S.N., Jeong, S.H., Stonik, V.A., Rasskazov, V.A., Zvyagintseva, T., Lee, Y.H. Fucoidan inhibits UVB-induced MMP-1 expression in human skin fibroblasts. Biol Pharm Bull, 31: 284-289, 2008. https://doi.org/10.1248/bpb.31.284
  12. Fisher, G.J., Datta, S.C., Talwar, H.S., Wang, Z.Q., Varani, J., Kang, S., Voorhees, J.J. Molecular basis of sun-induced premature skin ageing and retinoid antagonism. Nature, 379: 335-339, 1996. https://doi.org/10.1038/379335a0
  13. Chung, J.H., Seo, J.Y., Choi, H.R., Lee, M.K., Youn, C.S., Rhie, G., Cho, K.H., Kim, K.H., Park, K.C., Eun, H.C. Modulation of skin collagen metabolism in aged and photoaged human skin in vivo. J Invest Dermatol, 117: 1218-1224, 2001. https://doi.org/10.1046/j.0022-202x.2001.01544.x
  14. Chung, J.H., Seo, J.Y., Lee, M.K., Eun, H.C., Lee, J.H., Kang, S., Fisher, G.J., Voorhees, J.J. Ultraviolet modulation of human macrophage metalloelastase in human skin in vivo. J Invest Dermatol, 119: 507-512, 2002. https://doi.org/10.1046/j.1523-1747.2002.01844.x
  15. Pasparakis, M., Courtois, G., Hafner, M., Schmidt-Supprian, M., Nenci, A., Toksoy, A., Krampert, M., Goebeler, M., Gillitzer, R., Israel, A., Krieg, T., Rajewsky, K., Haase, I. TNF-mediated inflammatory skin disease in mice with epidermis-specific deletion of IKK2. Nature, 417: 861-866, 2002. https://doi.org/10.1038/nature00820
  16. Takao, J., Yudate, T., Das, A., Shikano, S., Bonkobara, M., Ariizumi, K., Cruz, P.D. Expression of NF-kappaB in epidermis and the relationship between NF-kappaB activation and inhibition of keratinocyte growth. Br J Dermatol, 148: 680-688, 2003. https://doi.org/10.1046/j.1365-2133.2003.05285.x
  17. Cooper, S.J., Bowden, G.T. Ultraviolet B regulation of transcription factor families: roles of nuclear factor-kappa B (NF-kappaB) and activator protein-1 (AP-1) in UVB-induced skin carcinogenesis. Curr Cancer Drug Targets, 7: 325-334, 2007. https://doi.org/10.2174/156800907780809714
  18. Bell, S., Degitz, K., Quirling, M., Jilg, N., Page, S., Brand, K. Involvement of NF-kappaB signalling in skin physiology and disease. Cell Signal, 15: 1-7, 2003. https://doi.org/10.1016/S0898-6568(02)00080-3
  19. Zhang, Y., Talalay, P., Cho, C.G., Posner, G.H. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci U S A, 89: 2399-2403, 1992. https://doi.org/10.1073/pnas.89.6.2399
  20. Gibbs, A., Schwartzman, J., Deng, V., Alumkal, J. Sulforaphane destabilizes the androgen receptor in prostate cancer cells by inactivating histone deacetylase 6. Proc Natl Acad Sci U S A, 106: 16663-16668, 2009. https://doi.org/10.1073/pnas.0908908106
  21. Fahey, J.W., Haristoy, X., Dolan, P.M., Kensler, T.W., Scholtus, I., Stephenson, K.K., Talalay, P., Lozniewski, A. Sulforaphane inhibits extracellular, intracellular, and antibiotic-resistant strains of Helicobacter pylori and prevents benzo[a]pyrene-induced stomach tumors. Proc Natl Acad Sci U S A, 99: 7610-7615, 2002. https://doi.org/10.1073/pnas.112203099
  22. Talalay, P., Fahey, J.W., Healy, Z.R., Wehage, S.L., Benedict, A.L., Min, C., Dinkova-Kostova, A.T. Sulforaphane mobilizes cellular defenses that protect skin against damage by UV radiation. Proc Natl Acad Sci U S A, 104: 17500-17505, 2007. https://doi.org/10.1073/pnas.0708710104
  23. Heiss, E., Herhaus, C., Klimo, K., Bartsch, H., Gerhauser, C. Nuclear factor kappa B is a molecular target for sulforaphane-mediated anti-inflammatory mechanisms. J Biol Chem, 276: 32008-32015, 2001. https://doi.org/10.1074/jbc.M104794200
  24. Song, M.Y., Kim, E.K., Moon, W.S., Park, J.W., Kim, H.J., So, H.S., Park, R., Kwon, K.B., Park, B.H. Sulforaphane protects against cytokine- and streptozotocin-induced beta-cell damage by suppressing the NF-kappaB pathway. Toxicol Appl Pharmacol, 235: 57-67, 2009. https://doi.org/10.1016/j.taap.2008.11.007
  25. Lee, Y.R., Noh, E.M., Jeong, E.Y., Yun, S.K., Jeong, Y.J., Kim, J.H., Kwon, K.B., Kim, B.S., Lee, S.H., Park, C.S., Kim, J.S. Cordycepin inhibits UVB-induced matrix metalloproteinase expression by suppressing the NF-kappaB pathway in human dermal fibroblasts. Exp Mol Med, 41: 548-554, 2009. https://doi.org/10.3858/emm.2009.41.8.060
  26. Bradford, M.M. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem, 72: 248-254, 1976. https://doi.org/10.1016/0003-2697(76)90527-3
  27. Uitto, J. Connective tissue biochemistry of the aging dermis. Age-related alterations in collagen and elastin. Dermatol Clin, 4: 433-446, 1986.
  28. Gilchrest, B.A. A review of skin ageing and its medical therapy, Br J Dermatol, 135: 867-875, 1996. https://doi.org/10.1046/j.1365-2133.1996.d01-1088.x
  29. Chung, J.H., Hanft, V.N., Kang, S. Aging and photoaging. J Am Acad Dermatol, 49: 690-697, 2003. https://doi.org/10.1067/S0190-9622(03)02127-3
  30. Varani, J., Perone, P., Fligiel, S.E., Fisher, G.J., Voorhees, J.J. Inhibition of type I procollagen production in photodamage: correlation between presence of high molecular weight collagen fragments and reduced procollagen synthesis. J Invest Dermatol, 119: 122-129, 2002. https://doi.org/10.1046/j.1523-1747.2002.01810.x
  31. Fisher, G.J., Wang, Z.Q., Datta, S.C., Varani, J., Kang, S., Voorhees, J.J. Pathophysiology of premature skin aging induced by ultraviolet light. N Engl J Med, 337: 1419-1428, 1997. https://doi.org/10.1056/NEJM199711133372003
  32. Gilchrest, B.A., Yaar, M. Ageing and photoageing of the skin: observations at the cellular and molecular level. Br J Dermatol, 127 Suppl 41: 25-30, 1992. https://doi.org/10.1111/j.1365-2133.1992.tb16984.x
  33. Saliou, C., Kitazawa, M., McLaughlin, L., Yang, J.P., Lodge, J.K., Tetsuka, T., Iwasaki, K., Cillard, J., Okamoto, T., Packer, L. Antioxidants modulate acute solar ultraviolet radiation-induced NF-kappa-B activation in a human keratinocyte cell line. Free Radic Biol Med, 26: 174-183, 1999. https://doi.org/10.1016/S0891-5849(98)00212-3
  34. Kim, J., Hwang, J.S., Cho, Y.K., Han, Y., Jeon, Y.J., Yang, K.H. Protective effects of (-)-epigallocatechin-3-gallate on UVA- and UVB-induced skin damage. Skin Pharmacol Appl Skin Physiol, 14: 11-19, 2001. https://doi.org/10.1159/000056329
  35. Adhami, V.M., Afaq, F., Ahmad, N. Suppression of ultraviolet B exposure-mediated activation of NF-kappaB in normal human keratinocytes by resveratrol. Neoplasia, 5: 74-82, 2003. https://doi.org/10.1016/S1476-5586(03)80019-2
  36. Tanaka, K., Hasegawa, J., Asamitsu, K., Okamoto, T. Prevention of the ultraviolet B-mediated skin photoaging by a nuclear factor kappaB inhibitor, parthenolide. J Pharmacol Exp Ther, 315: 624-630, 2005. https://doi.org/10.1124/jpet.105.088674
  37. Tanaka, K., Hasegawa, J., Asamitsu, K., Okamoto, T. Magnolia ovovata extract and its active component magnolol prevent skin photoaging via inhibition of nuclear factor kappaB. Eur J Pharmacol, 565: 212-219, 2007. https://doi.org/10.1016/j.ejphar.2007.01.095
  38. Bond, M., Baker, A.H., Newby, A.C. Nuclear factor kappaB activity is essential for matrix metalloproteinase-1 and -3 upregulation in rabbit dermal fibroblasts. Biochem Biophys Res Commun, 264: 561-567, 1999. https://doi.org/10.1006/bbrc.1999.1551
  39. Chung, J.H. Photoaging in Asians. Photodermatol Photoimmunol Photomed, 19: 109-121, 2003. https://doi.org/10.1034/j.1600-0781.2003.00027.x
  40. Thanos, D., Maniatis, T. NF-kappa B: a lesson in family values. Cell, 80: 529-532, 1995. https://doi.org/10.1016/0092-8674(95)90506-5