Molecules and Cells

  • 제25권4호
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  • Pages.531-537
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  • 2008
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  • 1016-8478(pISSN)
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  • 0219-1032(eISSN)
한국분자세포생물학회 (Korean Society for Molecular and Cellular Biology)
권호 표지

Curcumin Alleviates Dystrophic Muscle Pathology in mdx Mice

  • Pan, Ying (Model Animal Research Center, Medical School, Nanjing University) ;
  • Chen, Chen (Model Animal Research Center, Medical School, Nanjing University) ;
  • Shen, Yue (Huadong Research Institute for Medical Biotechnics) ;
  • Zhu, Chun-Hua (Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University) ;
  • Wang, Gang (Nanjing Children's Hospital) ;
  • Wang, Xiao-Chun (Huadong Research Institute for Medical Biotechnics) ;
  • Chen, Hua-Qun (Jiangsu Key Laboratory for Molecular and Medical Biotechnology, College of Life Science, Nanjing Normal University) ;
  • Zhu, Min-Sheng (Model Animal Research Center, Medical School, Nanjing University)
  • 투고 : 2007.10.29
  • 심사 : 2007.12.12
  • 발행 : 2008.06.30
⟨ 이전 논문 다음 논문 ⟩

초록

Abnormal activation of nuclear factor kappa B ($NF-{\kappa}B$) probably plays an important role in the pathogenesis of Duchenne's muscular dystrophy (DMD). In this report, we evaluated the efficacy of curcumin, a potent $NF-{\kappa}B$ inhibitor, in mdx mice, a mouse model of DMD. We found that it improved sarcolemmic integrity and enhanced muscle strength after intraperitoneal (i.p.) injection. Histological analysis revealed that the structural defects of myofibrils were reduced, and biochemical analysis showed that creatine kinase (CK) activity was decreased. We also found that levels of tumor necrosis factor alpha ($TNF-\alpha$), interleukin-1 beta ($IL-1\beta$) and inducible nitric oxide synthase (iNOS) in the mdx mice were decreased by curcumin administration. EMSA analysis showed that $NF-{\kappa}B$ activity was also inhibited. We thus conclude that curcumin is effective in the therapy of muscular dystrophy in mdx mice, and that the mechanism may involve inhibition of $NF-{\kappa}B$ activity. Since curcumin is a non-toxic compound derived from plants, we propose that it may be useful for DMD therapy.

키워드

과제정보

연구 과제 주관 기관 : National Natural Science Foundation of China

참고문헌

  1. Acharyya, S., Villalta, S.A., Bakkar, N., Bupha-Intr, T., Janssen, P.M., Carathers, M., Li, Z.W., Beg, A.A., Ghosh, S., Sahenk, Z., et al. (2007). Interplay of IKK/NF-{kappa}B signaling in macrophages and myofibers promotes muscle degeneration in Duchenne muscular dystrophy. J. Clin. Invest. 117, 889-901 https://doi.org/10.1172/JCI30556
  2. Aggarwal, B.B., Kumar, A., and Bharti, A.C. (2003). Anticancer potential of curcumin: preclinical and clinical studies. Anticancer Res. 23, 363-398
  3. Ammon, H.P., and Wahl, M.A. (1991). Pharmacology of Curcuma longa. Planta Med. 57, 1-7 https://doi.org/10.1055/s-2006-960004
  4. Araujo, C.C., and Leon, L.L. (2001). Biological activities of Curcuma longa L. Mem. Inst. Oswaldo Cruz 96, 723-728 https://doi.org/10.1590/S0074-02762001000500026
  5. Belzung, C., Guisquet, A.M., Barreau, S., and Calatayud, F. (2001). An investigation of the mechanisms responsible for acute fluoxetine-induced anxiogenic-like effects in mice. Behav. Pharmacol. 12, 151-162 https://doi.org/10.1097/00008877-200105000-00001
  6. Blake, D.J., Tinsley, J.M., and Davies, K.E. (1996). Utrophin: a structural and functional comparison to dystrophin. Brain Pathol. 6, 37-47 https://doi.org/10.1111/j.1750-3639.1996.tb00781.x
  7. Cai, D., Frantz, J.D., Melendez, P.A., Oh, B.C., Lidov, H.G., Hasselgren, P.O., Frontera, W.R., Lee, J., Glass, D.J., and Shoelson, S.E. (2004). IKKbeta/NF-kappaB activation causes severe muscle wasting in mice. Cell 119, 285-298 https://doi.org/10.1016/j.cell.2004.09.027
  8. Cammer, M., Minetti, C., and Lisanti, M.P. (2003). Proteasome inhibitor (MG-132) treatment of mdx mice rescues the expression and membrane localization of dystrophin and dystrophin-associated proteins. Am. J. Pathol. 163, 1663-1675 https://doi.org/10.1016/S0002-9440(10)63523-7
  9. Das, K.C., and Das, C.K. (2002). Curcumin (diferuloylmethane), a singlet oxygen (1O2) quencher. Biochem. Biophys. Res. Commun. 95, 2-6
  10. Disatnik, M.H., Chamberlain, J.S., and Rando, T.A. (2000). Dystrophin mutations predict cellular susceptibility to oxidative stress. Muscle Nerve 23, 784-792 https://doi.org/10.1002/(SICI)1097-4598(200005)23:5<784::AID-MUS17>3.0.CO;2-Y
  11. Durham, W.J., Arbogast, S., Gerken, E., Li, Y.P., and Reid, M.B. (2006). Progressive nuclear factor-kB activation resistant to inhibition by contraction and curcumin in mdx mice. Muscle Nerve 34, 298-303 https://doi.org/10.1002/mus.20579
  12. Ghosh, S., May, M.J., and Kopp, E.B. (1998). NF-kappaB and Rel proteins: evolutionarily conserved mediators of immune responses. Annu. Rev. Immunol. 6, 25-60 https://doi.org/10.1146/annurev.iy.06.040188.000325
  13. Griscavage, J.M., Hobbs, A.J., and Ignarro, L.J. (1995). Negative modulation of nitric oxide synthase by nitric oxide and nitroso compounds. Adv. Pharmacol. 34, 215-234 https://doi.org/10.1016/S1054-3589(08)61088-1
  14. Grounds, M.D., and Torrisi, J. (2004). Anti-TNFalpha (Remicade) therapy protects dystrophic skeletal muscle from necrosis. FASEB J. 18, 676-682 https://doi.org/10.1096/fj.03-1024com
  15. Hamed, S.A. (2006). Drug evaluation: PTC-124--a potential treatment of cystic fibrosis and Duchenne muscular dystrophy. I. Drugs. 9, 783-789
  16. Hoffman, E.P., Brown, R.H. Jr., and Kunkel, L.M. (1987). Dystrophin: the protein product of the Duchenne muscular dystrophy locus. Cell 51, 919-928 https://doi.org/10.1016/0092-8674(87)90579-4
  17. Hoffman, E.P., Fischbeck, K.H., Brown, R.H., Johnson, M., Medori, R., Loike, J.D., Harris, J.B., Waterston, R., Brooke, M., Specht, L., et al. (1988). Characterization of dystrophin in muscle-biopsy specimens from patients with Duchenne's or Becker's muscular dystrophy. N. Engl. J. Med. 318, 1363-1368 https://doi.org/10.1056/NEJM198805263182104
  18. Hunter, R.B., and Kandarian, S.C. (2004). Disruption of either the Nfkb1 or the Bcl3 gene inhibits skeletal muscle atrophy. J. Clin. Invest. 114, 1504-1511 https://doi.org/10.1172/JCI200421696
  19. Koenig, M., Hoffman, E.P., Bertelson, C.J., Monaco, A.P., Feener, C., and Kunkel, L.M. (1987). Complete cloning of the Duchenne muscular dystrophy (DMD) cDNA and preliminary genomic organization of the DMD gene in normal and affected individuals. Cell 50, 509-517 https://doi.org/10.1016/0092-8674(87)90504-6
  20. Kumar, A., and Boriek, A.M. (2003). Mechanical stress activates the nuclear factor-kappaB pathway in skeletal muscle fibers: a possible role in Duchenne muscular dystrophy. FASEB J. 17, 386-396 https://doi.org/10.1096/fj.02-0542com
  21. Lapidos, K.A., Kakkar, R., and McNally, E.M. (2004). The dystrophin glycoprotein complex signaling strength and integrity for the sarcolemma. Circ. Res. 94, 1023-1031 https://doi.org/10.1161/01.RES.0000126574.61061.25
  22. Louboutin, J.P., Rouger, K., Tinsley, J.M., Halldorson, J., and Wilson, J.M. (2001). iNOS expression in dystrophinopathies can be reduced by somatic gene transfer of dystrophin or utrophin. Mol. Med. 7, 355-364
  23. Lundberg, I., Brengman, J.M., and Engel, A.G. (1995). Analysis of cytokine expression in muscle in inflammatory myopathies, Duchenne dystrophy, and non-weak controls. J. Neuroimmunol. 63, 9-16 https://doi.org/10.1016/0165-5728(95)00122-0
  24. Mahmmoud, Y.A. (2005). Curcumin modulation of Na,K-ATPase: phosphoenzyme accumulation, decreased K+ occlusion, and inhibition of hydrolytic activity. Br. J. Pharmacol. 145, 236-245 https://doi.org/10.1038/sj.bjp.0706185
  25. Matsumura, K., and Campbell, K.P. (1994). Dystrophin-glycoprotein complex: its role in the molecular pathogenesis of muscular dystrophies. Muscle Nerve 17, 2-15 https://doi.org/10.1002/mus.880170103
  26. Meyer, O.A., Tilson, H.A., Byrd, W.C., and Riley, M.T. (1979). A method for the routine assessment of fore- and hindlimb grip strength of rats and mice. Neurobehav. Toxicol. 1, 233-236
  27. Monaco, A.P., Neve, R.L., Colletti-Feener, C., Bertelson, C.J., Kurnit, D.M., and Kunkel, L.M. (1986). Isolation of candidate cDNAs for portions of the Duchenne muscular dystrophy gene. Nature 323, 646-650 https://doi.org/10.1038/323646a0
  28. Murugesan, T., Saravanan, K.S., Lakshmi, S., and Ramya, G. (2001). Thenmozhi K: evaluation of psychopharmacological effects of clerodendrum phlomidis Linn. Extract Phytomedicine 8, 472-476 https://doi.org/10.1078/S0944-7113(04)70068-9
  29. Nowak, K.J., and Davies, K.E. (2004). Duchenne muscular dystrophy and dystrophin: pathogenesis and opportunities for treatment. EMBO Rep. 5, 872-876 https://doi.org/10.1038/sj.embor.7400221
  30. Oak, S.A., Zhou, Y.W., and Jarrett, H.W. (2003). Skeletal muscle signaling pathway through the dystrophin glycoprotein complex and Rac1. J. Biol. Chem. 278, 39287-39295 https://doi.org/10.1074/jbc.M305551200
  31. Pan, M.H., Lin-Shiau, S.Y., and Lin, J.K. (2000). Comparative studies on the suppression of nitric oxide synthase by curcumin and its hydrogenated metabolites through down-regulation of IkappaB kinase and NFkappaB activation in macrophages. Biochem. Pharmacol. 60, 1665-1676 https://doi.org/10.1016/S0006-2952(00)00489-5
  32. Pasternak, C., Wong, S., and Elson, E.L. (1995). Mechanical function of dystrophin in muscle cells. J. Cell. Biol. 128, 355-361 https://doi.org/10.1083/jcb.128.3.355
  33. Rando, T.A., Disatnik, M.H., Yu, Y., and Franco, A. (1998). Muscle cells from mdx mice have an increased susceptibility to oxidative stress. Neuromuscul. Disord. 8, 14-21 https://doi.org/10.1016/S0960-8966(97)00124-7
  34. Sadoulet-Puccio, H.M. and Kunkel, L.M. (1996). Dystrophin and its isoforms. Brain Pathol. 6, 25-35 https://doi.org/10.1111/j.1750-3639.1996.tb00780.x
  35. Salvemini, D., and Marino, M.H. (1998). Inducible nitric oxide synthase and inflammation. Expert Opin. Investig. Drugs 7, 65-75 https://doi.org/10.1517/13543784.7.1.65
  36. Shishodia, S., Potdar, P., Gairola, C.G., and Aggarwal, B.B. (2003). Curcumin (diferuloylmethane) down-regulates cigarette smokeinduced NF-kappaB activation through inhibition of Ikappa-Balpha kinase in human lung epithelial cells: correlation with suppression of COX-2, MMP-9 and cyclin D1. Carcinogenesis 24, 1269-1279 https://doi.org/10.1093/carcin/bgg078
  37. Spence, H.J., Dhillon, A.S., James, M., and Winder, S.J. (2004). Dystroglycan, a scaffold for the ERK-MAP kinase cascade. EMBO Rep. 5, 484-489 https://doi.org/10.1038/sj.embor.7400140
  38. St-Pierre, S.J., Chakkalakal, J.V., Kolodziejczyk, S.M., Knudson, J.C., Jasmin, B.J., and Megeney, L.A. (2004). Glucocorticoid treatment alleviates dystrophic myofiber pathology by activation of the calcineurin/NF-AT pathway. FASEB J. 18, 1937-1939 https://doi.org/10.1096/fj.04-1859fje
  39. Straub, V., Rafael, J.A., Chamberlain, J.S., and Campbell, K.P. (1997). Animal models for muscular dystrophy show different pattern of sarcolemmal disruption. J. Cell. Biol. 139, 375-385 https://doi.org/10.1083/jcb.139.2.375
  40. Tinsley, J.M., Blake, D.J., Zuellig, R.A., and Davies, K.E. (1994). Increasing complexity of the dystrophin-associated protein complex. Proc. Natl. Acad. Sci. USA 91, 8307-8313
  41. Villar, R., Laguna, M.R., Calleja, J.M., and Cadavid, I. (1992). Effects of Skeletonema costatum extracts on the central nervous system. Planta Med. 58, 398-403 https://doi.org/10.1055/s-2006-961500
  42. Yang, K.Y., Lin, L.C., Tseng, T.Y., Wang, S.C., and Tsai, T.H. (2007). Oral bioavailability of curcumin in rat and the herbal analysis from curcuma longa by LC-MS/MS. J. Chromatogr. B. Analyt. Technol. Biomed. Life Sci. 853, 183-189 https://doi.org/10.1016/j.jchromb.2007.03.010
  43. Zhu, M.S., Pan, Y., Chen, H.Q., Shen, Y., Wang, X.C., Sun, Y.J., and Tao, K.H. (2004). Induction of SARS-nucleoprotein-specific immune response by use of DNA vaccine. Immunol. Lett. 92, 237-243 https://doi.org/10.1016/j.imlet.2004.01.001