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Phospho-ser 15-p53 translocates into mitochondria and interacts with Bcl-2 and Bcl-xL in eugenol-induced apoptosis

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Abstract

Our previous studies demonstrated that antiallergic effects of herbs such as clove and Magnoliae Flos (MF) resulted from the induction of apoptosis in mast cells. We here examined whether the antiallergic activity was caused by eugenol (4-allyl-2-methoxyphenol) which was one of major ingredients in the essential oils or extracts of numerous plants including clove and Magnoliae Flos. RBL-2H3 cells were treated with eugenol, and DNA electrophoresis, Western blotting, immunocytochemistry, confocal microscopy and immunoprecipitation were conducted. Effect of eugenol was tested using a rat anaphylaxis model. RBL-2H3 cells treated with eugenol showed typical apoptotic manifestations and translocation of p53 into mitochondria. Antisense p53 partially prevented the induction of apoptosis. Noticeably, we observed that p53 translocated into mitochondria was phosphorylated on ser 15. Phospho-ser 15-p53 physically interacted with Bcl-2 and Bcl-xL in mitochondria and its translocation into mitochondria preceded cytochrome c release and mitochondrial membrane potential (MMP) reduction. We also depicted that the survival of animals even after administration of the fatal dose of compound 48/80 might result from the decreased number of mast cells by eugenol pretreatment. In conclusion, eugenol induces apoptosis in mast cells via translocation of phospho-ser 15-p53 into mitochondria.

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References

  1. Ohta K, Yamashita N. Apoptosis of eosinophils and lymphocytes in allergic inflammation. J Allergy Clin Immunol 1999; 104: 14–21.

    PubMed  CAS  Google Scholar 

  2. Carson DA, Ribeiro JM. Apoptosis and disease. Lancet 1993; 341: 1251–1254.

    PubMed  CAS  Google Scholar 

  3. Williams GT. Programmed cell death: Apoptosis and oncogenesis. Cell 1991; 65: 1097–1098.

    PubMed  CAS  Google Scholar 

  4. Thornberry NA, Rosen A, Nicholson DW. Control of apoptosis by proteases. Adv In Pharmacol 1997; 41: 155–177.

    Article  CAS  Google Scholar 

  5. Green DR, Reed JC. Mitochondria and apoptosis. Science 1998; 281: 1309–1312.

    Article  CAS  PubMed  Google Scholar 

  6. Hart PH. Regulation of the inflammatory response in asthma by mast cell products. Immunol Cell Biol 2001; 79: 149–153.

    PubMed  CAS  Google Scholar 

  7. Bachert C. The role of histamine in allergic disease: Re-appraisal of its inflammatory potential. Allergy 2002; 57: 287–296.

    PubMed  CAS  Google Scholar 

  8. Metcalfe DD, Mekori JA, Rottem M. Mast cell ontogeny and apoptosis. Exp Dermatol 1995; 4: 227–230.

    PubMed  CAS  Google Scholar 

  9. Fuller R, Johnson M, Bye A. Fluticasone propionate-an update on preclinical and clinical experience. Res Pir Med 1995; 89: 3–18.

    Google Scholar 

  10. Park HI, Jeong MH, Lim YJ, et al. Szygium aromaticum (L.) Merr. Et Perry (Myrtaceae) flower bud induces apoptosis of p815 mastocytoma cell line. Life Sci 2001; 69: 553–556.

    PubMed  CAS  Google Scholar 

  11. Kim GC, Lee SG, Park BS, et al. Magnoliae flos induces apoptosis of RBL-2H3 cells via mitochondria and caspase. Int Arch Allergy Immunol 2003; 131: 101–110.

    PubMed  Google Scholar 

  12. IARC Monographs Evaluation of the carcinogenic risk of chemicals to humans. France: Lyon IARC Press, 1985; 36: 75.

  13. Zhu YP. Materia Medica: Chemistry, Pharmacology and Applications Harwood. Amsterdam: Academic Publishers, 1996: 1

  14. Cao Y, Cao R. Angiogenesis inhibited by drinking tea. Nature 1999; 398: 381.

    PubMed  CAS  Google Scholar 

  15. Bai X, Cerimele F, Ushio-Fukai M, et al. Honokiol, a small molecular weight natural product, inhibits angiogenesis in vitro and tumor growth in vivo. J Biol Chem 2003; 278: 35501–35507.

    PubMed  CAS  Google Scholar 

  16. Kim HM, Lee EH, Kim CY, et al. Antianaphylactic properties of eugenol. Pharmacol Res 1997; 36: 475–480.

    PubMed  CAS  Google Scholar 

  17. Shin BK, Lee EH, Kim HM. Suppression of L-histidine decarboxylase mRNA expression by methyleugenol. Biochem Biophys Res Commun 1997; 232: 188–191.

    PubMed  CAS  Google Scholar 

  18. Johnstone RW, Ruefli AA, Lowe SW. Apoptosis: A link between cancer genetics and chemotherapy. Cell 2002; 108: 153–164.

    CAS  PubMed  Google Scholar 

  19. Nakano K, Vousden KH. PUMA, a novel proapoptotic gene, is induced by p53. Mol Cell 2001;7: 683–694.

    PubMed  CAS  Google Scholar 

  20. Wagner AJ, Kokontis JM, Hay N. Myc-mediated apoptosis requires wild-type p53 in a manner independent of cell cycle arrest and the ability of p53 to induce p21waf1/cip1. Genes Dev 1994; 8: 2817–2830.

    PubMed  CAS  Google Scholar 

  21. Marchenko ND, Zaika A, Moll UM. Death signal-induced localization of p53 protein to mitochondria. A potential role in apoptotic signaling. J Biol Chem 2000; 275: 16202–16212.

    PubMed  CAS  Google Scholar 

  22. Mihara M, Erster S, Zaika A, et al. p53 has a direct apoptogenic role at the mitochondria. Mol Cell 2003; 11: 577–590.

    Article  CAS  PubMed  Google Scholar 

  23. Baptiste N, Prives C. p53 in the cytoplasm: A question of overkill. Cell 2004; 116: 487–489.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Oral Anatomy and Cell Biology, Pusan National University College of Dentistry, Busan, South Korea

    B. S. Park

  2. Department of Anatomy and Cell Biology (BK21 program), Busan, South Korea

    Y. S. Song, S.-B. Yee, B. G. Lee, Y. C. Park, J.-M. Kim & Y. H. Yoo

  3. Department of Microbiology and Immunology, Busan, South Korea

    S. Y. Seo

  4. Department of Pharmacology, College of Oriental Medicine, Kyung Hee University, Seoul, South Korea

    H. M. Kim

Authors
  1. B. S. Park
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  2. Y. S. Song
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  3. S.-B. Yee
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  4. B. G. Lee
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  5. S. Y. Seo
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  6. Y. C. Park
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  7. J.-M. Kim
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  8. H. M. Kim
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  9. Y. H. Yoo
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Corresponding author

Correspondence to Y. H. Yoo.

Additional information

The contribution of Yeon Suk Song to the manuscript is equal to that of Bong Soo Park

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Park, B.S., Song, Y.S., Yee, SB. et al. Phospho-ser 15-p53 translocates into mitochondria and interacts with Bcl-2 and Bcl-xL in eugenol-induced apoptosis. Apoptosis 10, 193–200 (2005). https://doi.org/10.1007/s10495-005-6074-7

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  • DOI: https://doi.org/10.1007/s10495-005-6074-7

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