생명과학회지 (Journal of Life Science)

  • 제21권5호
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  • Pages.693-699
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  • 2011
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  • 1225-9918(pISSN)
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  • 2287-3406(eISSN)
한국생명과학회 (Korean Society of Life Science)
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사람피부섬유아세포에서 산화적 스트레스에 대한 항산화 활성을 가진 spermidine의 억제효과

Inhibitory Effect of Spermidine with Antioxidant Activity on Oxidative Stress in Human Dermal Fibroblasts

  • 투고 : 2011.01.26
  • 심사 : 2011.02.09
  • 발행 : 2011.05.30
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초록

Spermidine은 spermine의 전구체로 역할을 하는 putrescine로부터 합성되는 polycation의 한 형태이다. 최근에 spermidine는 수명연장에 중요한 역할을 하는 하나의 polyamine으로 알려져 있다. Hydroxyl radical, superoxide 및 hydrogen peroxide와 같은 활성산소(ROS)는 노화뿐만 아니라 다양한 병원성 과정에서 관여한다고 보고되고 있다. DPPH radical, $H_2O_2$ 및 hydroxyl radical에 대한 spermidine의 소거활성과 산화적 스트레스와 관련된 DNA oxidation에 대한 보호 효과가 in-vitro에서 평가되었다. Spermidine은 500 ${\mu}M$ 이상에서 DPPH radical와 $H_2O_2$에 대한 소거 효과를 보여주었다. 특히 활성산소종 중에서 spermidine는 hydroxyl radical에 대한 효과가 탁월하였다. 뿐만 아니라, spermidine는 500 ${\mu}M$에서 DNA oxidation에 대해서도 뚜렷한 보호 효과를 나타내었다. 더욱이 사람피부섬유아세포에서 superoxide dismutase와 같은 항산화 관련 단백질의 발현이 대조군과 비교시 spermidine 존재 하에 증가하였다. 이상의 결과로부터 spermidine은 암, 노화 및 염증을 포함하는 활성산소와 관련 있는 질병들을 예방하기 위한 항산화제로 이용될 수 있을 것이다.

Spermidine is a ubiquitous polycation that is synthesized from putrescine, which serves as a precursor of spermine. In recent years, spermidine was found to be a polyamine that plays an important role in longevity. Reactive oxygen species (ROS) such as hydroxyl radical, superoxide and hydrogen peroxide have been shown to be involved in various pathogenic processes as well as aging. The direct scavenging effect of spermidine on DPPH radical, $H_2O_2$ and hydroxyl radical, and its protective effect against DNA oxidation related to oxidative stress were evaluated in vitro. It was observed that spermidine exhibits scavenging activities on DPPH radical and H2O2 above 500 ${\mu}M$. Spermidine was especially effective in exerting a scavenging activity on hydroxyl radical. In addition, spermidine at 1000 ${\mu}M$ showed a clear protective effect against DNA oxidation. Furthermore, the expression level of anti-oxidant enzymes such as superoxide dismutase in humam dermal fibroblasts increased in the presence of spermidine compared with blank group. These results suggest that spermidine can be used as an antioxidant to prevent ROS-related diseases including inflammation, cancer and aging.

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참고문헌

  1. Bouchereau, A., A. Aziz, F, Larher, and J. Martin-Tanguy. 1999. Polyamines and environmental challenges: recent development. Plant Sci. 140, 103-125. https://doi.org/10.1016/S0168-9452(98)00218-0
  2. Branen, A. 1975. Toxicology and biochemistry of butylated hydroxyanisole and butylated hydroxytoluene. J. Am. Oil. Chem Soc. 52, 59-63. https://doi.org/10.1007/BF02901825
  3. Choi, C. W., S. C. Kim, S. S. Hwang, B. K. Choi, H. J. Ahn, M. Y. Lee, S. H. Park, and S. K. Kim. 2002. Antioxidant activity and free radical scavenging capacity between Korean medicinal plants and flavonoids by assay-guided comparison. Plant Sci. 163, 1161-1168. https://doi.org/10.1016/S0168-9452(02)00332-1
  4. Choi, C. S., E. S. Song, J. S. Kim, and M. H. Kang. 2003. Antioxidative activities of Castanea crenata Flos. methanol extracts. Korean J. Food Sci. Technol. 35, 1216-1220.
  5. Cuevas, J., R. Lopez-Cobollo, R. Alcazar, X. Zarza, C. Koncz, T. Altabella, J. Salinas, A. Tiburcio, and A. Ferrando. 2008. Putrescine is involved in Arabidopsis freezing tolerance and cold acclimation by regulating abscisic acid levels in response to low temperature. Plant Physiol. 148, 1094-1105. https://doi.org/10.1104/pp.108.122945
  6. Davies, P. 2010. The plant hormones: their nature, occurrence, and functions. Plant Hormones A, 1-15.
  7. Duan, J., J. Li, S. Guo, and Y. Kang. 2008. Exogenous spermidine affects polyamine metabolism in salinity-stressed Cucumis sativus roots and enhances short-term salinity tolerance. J. Plant Physiol. 165, 1620-1635. https://doi.org/10.1016/j.jplph.2007.11.006
  8. Eisenberg, T., H. Knauer, A. Schauer, S. Buttner, C. Ruckenstuhl, D. Carmona-Gutierrez, J. Ring, S. Schroeder, C. Magnes, and L. Antonacci. 2009. Induction of autophagy by spermidine promotes longevity. Nat. Cell Biol. 11, 1305-1314. https://doi.org/10.1038/ncb1975
  9. Feuerstein, B. and L. Marton. 1989. Specificity and binding in polyamine/nucleic acid interactions. pp. 109-124, In Bachrach, U. and Y. M. Heimer (eds.), The Physiology of Polyamines, CRC Press, Boca Raton, Florida.
  10. Galston, A. 2001. Plant biology-Retrospect and prospect. Curr. Sci. 80, 143-152.
  11. Groppa, M., M. Benavides, and M. Tomaro. 2003. Polyamine metabolism in sunflower and wheat leaf discs under cadmium or copper stress. Plant Sci. 164, 293-299. https://doi.org/10.1016/S0168-9452(02)00412-0
  12. Ha, H., N. Sirisoma, P. Kuppusamy, J. Zweier, P. Woster, and R. Casero. 1998. The natural polyamine spermine functions directly as a free radical scavenger. Proc. Natl. Acad. Sci. USA 95, 11140-11145. https://doi.org/10.1073/pnas.95.19.11140
  13. Hansen, M., S. Nielsen, and K. Berg. 1989. Re-examination and further development of a precise and rapid dye method for measuring cell growth/cell kill. J. Immunol. Methods 119, 203-210. https://doi.org/10.1016/0022-1759(89)90397-9
  14. Harman, D. 1956. A theory based on free radical and radiation chemistry. J. Gerontol. 11, 298-300. https://doi.org/10.1093/geronj/11.3.298
  15. Hasani-Ranjbar, S., B. Larijani, and M. Abdollahi. 2009. A systematic review of the potential herbal sources of future drugs effective in oxidant-related diseases. Inflamm Allergy Drug Targets 8, 2-10. https://doi.org/10.2174/187152809787582561
  16. Imai, J., N. Ide, S. Nagae, T. Moriguchi, H. Matsuura, and Y. Itakura. 1994. Antioxidant and radical scavenging effects of aged garlic extract and its constituents. Planta Med. 60, 417-420. https://doi.org/10.1055/s-2006-959522
  17. Jang, M., L. Cai, G. Udeani, K. Slowing, C. Thomas, C. Beecher, H. Fong, N. Farnsworth, A. Kinghorn, and R. Mehta. 1997. Cancer chemopreventive activity of resveratrol, a natural product derived from grapes. Science 275, 218-220. https://doi.org/10.1126/science.275.5297.218
  18. Khan, A., P. Di Mascio, M. Medeiros, and T. Wilson. 1992. Spermine and spermidine protection of plasmid DNA against single-strand breaks induced by singlet oxygen. Proc. Natl. Acad. Sci. USA 89, 11428-11430. https://doi.org/10.1073/pnas.89.23.11428
  19. Kitada, M., Y. Naito, K. Igarashi, S. Hirose, Y. Kanakubo, and H. Kitagawa. 1981. Possible mechanism of inhibition by polyamines of lipid peroxidation in rat liver microsomes. Res. Commun. Chem. Pathol. Pharmacol. 33, 487-497.
  20. Krishna, M., W. DeGraff, O. Hankovszky, C. Sar, T. Kalai, J. Jeko, A. Russo, J. Mitchell, and K. Hideg. 1998. Studies of structure- activity relationship of nitroxide free radicals and their precursors as modifiers against oxidative damage. J. Med. Chem. 41, 3477-3492. https://doi.org/10.1021/jm9802160
  21. Kwon, G. J., D. S. Choi, and M. H. Wang. 2007. Biological activities of hot water extracts from euonymus alatus leaf. Korean J. Food Sci. Technol. 39, 569-574.
  22. Lovaas, E. 1995. Hypothesis: spermine may be an important epidermal antioxidant. Medical Hypotheses 45, 59-67. https://doi.org/10.1016/0306-9877(95)90204-X
  23. Li, H., S. Yashiki, J. Sonoda, H. Lou, S. Ghosh, J. Byrnes, C. Lema, T. Fujiyoshi, M. Karasuyama, and S. Sonoda. 2000. Green tea polyphenols induce apoptosis in vitro in peripheral blood T lymphocytes of adult T-cell leukemia patients. Cancer Sci. 91, 34-40. https://doi.org/10.1111/j.1349-7006.2000.tb00857.x
  24. Lightfoot, T., C. Skibola, A. Smith, M. Forrest, P. Adamson, G. Morgan, P. Bracci, E. Roman, M. Smith, and E. Holly. 2006. Polymorphisms in the oxidative stress genes, superoxide dismutase, glutathione peroxidase and catalase and risk of non-Hodgkin's lymphoma. Haematologica. 91, 1222-12227.
  25. Looi, M., A. Mohd Dali, S. Md Ali, W. Wan Ngah, and Y. Mohd Yusof. 2008. Oxidative damage and antioxidant status in patients with cervical intraepithelial neoplasia and carcinoma of the cervix. Eur. J. Cancer Prev. 17, 555-560. https://doi.org/10.1097/CEJ.0b013e328305a10b
  26. Manian, R., N. Anusuya, P. Siddhuraju, and S. Manian. 2008. The antioxidant activity and free radical scavenging potential of two different solvent extracts of Camellia sinensis (L.) O. Kuntz, Ficus bengalensis L. and Ficus racemosa L. Food Chem. 107, 1000-1007. https://doi.org/10.1016/j.foodchem.2007.09.008
  27. Medic-Saric, M., V. Rastija, M. Boji, and Z. Male. 2009. From functional food to medicinal product: Systematic approach in analysis of polyphenolics from propolis and wine. Nutr. J. 8, 33.
  28. Milne, L., P. Nicotera, S. Orrenius, and M. Burkitt. 1993. Effects of glutathione and chelating agents on copper-mediated DNA oxidation: pro-oxidant and antioxidant properties of glutathione. Arch. Biochem. Biophys. 304, 102-109. https://doi.org/10.1006/abbi.1993.1327
  29. Moinard, C., L. Cynober, and J. de Bandt 2005. Polyamines: metabolism and implications in human diseases. Clin. Nutr. 24, 184-197. https://doi.org/10.1016/j.clnu.2004.11.001
  30. Mozdzan, M., J. Szemraj, J. Rysz, R. Stolarek, and D. Nowak. 2006. Anti-oxidant activity of spermine and spermidine re-evaluated with oxidizing systems involving iron and copper ions. Int. J. Biochem. Cell Biol. 38, 69-81. https://doi.org/10.1016/j.biocel.2005.07.004
  31. Ohnishi, N. and T. Yokoyama. 2004. Interactions between medicines and functional foods or dietary supplements. Keio. J. Med. 53, 137-150. https://doi.org/10.2302/kjm.53.137
  32. Oyaizu, M. 1986. Studies on products of the browning reaction. Antioxidative activities of browning reaction products prepared from glucosamine. Jpn. J. Nutr. 44, 307-315. https://doi.org/10.5264/eiyogakuzashi.44.307
  33. Reddy, A. and B. Lokesh. 1994. Studies on the inhibitory effects of curcumin and eugenol on the formation of reactive oxygen species and the oxidation of ferrous iron. Mol. Cell Biochem. 137, 1-8. https://doi.org/10.1007/BF00926033
  34. Rider, J., A. Hacker, C. Mackintosh, A. Pegg, P. Woster, and R. Casero. 2007. Spermine and spermidine mediate protection against oxidative damage caused by hydrogen peroxide. Amino Acids 33, 231-240. https://doi.org/10.1007/s00726-007-0513-4
  35. Sambrook, J., E. Fritsch, and T. Maniatis. 1989. Molecular cloning: A laboratory manual. pp. 1-344, 3th eds., Cold Spring Harbor Laboratory Press. New York.
  36. Valko, M., D. Leibfritz, J. Moncol, M. Cronin, M. Mazur, and J. Telser. 2007. Free radicals and antioxidants in normal physiological functions and human disease. Int. J. Biochem. Cell Biol. 39, 44-84. https://doi.org/10.1016/j.biocel.2006.07.001
  37. Yang, Y. H., Y. J. Kim, and H. Y. Chung. 2001. Peroxynitrite and hydroxyl radical scavenging activity of dihydroxybenzaldehydes. Korean J. Gerontol. 11, 24-28.
  38. Yoshiki, Y., M. Kinumi, T. Kahara, and K. Okubo. 1996. Chemiluminescence of soybean saponins in the presence of active oxygen species. Plant Sci. 116, 125-129. https://doi.org/10.1016/0168-9452(96)04375-0
  39. Zhao, H. and H. Yang. 2008. Exogenous polyamines alleviate the lipid peroxidation induced by cadmium chloride stress in Malus hupehensis Rehd. Sci. Hortic-Amsterdam. 116, 442-447. https://doi.org/10.1016/j.scienta.2008.02.017

피인용 문헌

  1. Polyamine Metabolism and Oxidative Protein Folding in the ER as ROS-Producing Systems Neglected in Virology vol.19, pp.4, 2018, https://doi.org/10.3390/ijms19041219