약학회지 (YAKHAK HOEJI)

  • 제58권4호
  • /
  • Pages.223-228
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  • 2014
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  • 0377-9556(pISSN)
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  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
권호 표지

브로콜리 유래 Sulforaphane의 혈관 수축성 조절 효과

The Inhibitory Effect of Broccoli in Cruciferous Vegetables Derived-Sulforaphane on Vascular Tension

  • 제현동 (대구가톨릭대학교 약학대학 약물학교실)
  • Je, Hyun Dong (Department of Pharmacology, College of Pharmacy, Catholic University of Daegu)
  • 투고 : 2014.05.16
  • 심사 : 2014.08.22
  • 발행 : 2014.08.30
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초록

The present study was undertaken to investigate the influence of sulforaphane on vascular smooth muscle contractility and to determine the mechanism involved. We hypothesized that sulforaphane, the primary ingredient of broccoli of cruciferous vegetables, plays a role in vascular relaxation through inhibition of Rho-kinase in rat aortae. Intact of denuded arterial rings from male Sprague-Dawley rats were used and isometric tensions were recorded using a computerized data acquisition system. Interestingly, sulforaphane significantly inhibited fluoride, phorbol ester or thromboxane $A_2$ mimetic-induced contraction in denuded muscles suggesting that additional pathways different from endothelial nitric oxide synthesis such as inhibition of Rho-kinase or MEK might be involved in the vasorelaxation. Furthermore, sulforaphane inhibited thromboxane $A_2$-induced increases in pERK1/2 levels suggesting the mechanism including inhibition of thromboxane $A_2$-induced increases in ERK1/2 phosphorylation. This study provides evidence that sulforaphane induces vascular relaxation through inhibition of Rho-kinase or MEK in rat aortae.

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참고문헌

  1. Lydakis, C., Lip, G. Y. H., Beevers, M. and Beevers, D. G. : Diet, lifestyle and blood pressure. Coronary Health Care 1, 130 (1997). https://doi.org/10.1016/S1362-3265(97)80003-X
  2. Marn, C., Yubero-Serrano, E. M., Lpez-Miranda, J. and Prez- Jimnez, F. : Endothelial aging associated with oxidative stress can be modulated by a healthy mediterranean diet. Int. J. Mol. Sci. 14, 8869 (2013). https://doi.org/10.3390/ijms14058869
  3. Favero, G., Paganelli, C., Buffoli, B., Rodella, L. F. and Rezzani, R. : Endothelium and its alterations in cardiovascular diseases: life style intervention. Biomed. Res. Int. in press (2014).
  4. Zhang, Y., Talalay, P., Cho, C. G. and Posner, G. H. : A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc. Natl. Acad. Sci. USA 89, 2399 (1992). https://doi.org/10.1073/pnas.89.6.2399
  5. Zhao, H. D., Zhang, F., Shen, G., Li, Y. B., Li, Y. H., Jing, H. R., Ma, L. F., Yao, J. H. and Tian, X. F. : Sulforaphane protects liver injury induced by intestinal ischemia reperfusion through Nrf2-ARE pathway. World J. Gastroenterol. 16, 3002 (2010). https://doi.org/10.3748/wjg.v16.i24.3002
  6. Piao, C. S., Gao, S., Lee, G. H., Kim, D. S., Park, B. H., Chae, S. W., Chae, H. J. and Kim, S. H. : Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K (ATP) channels. Pharmacol. Res. 61, 342 (2010). https://doi.org/10.1016/j.phrs.2009.11.009
  7. Zhao, J., Kobori, N., Aronowski, J. and Dash, P. K. : Sulforaphane reduces infarct volume following focal cerebral ischemia in rodents. Neurosci. Lett. 393, 108 (2006). https://doi.org/10.1016/j.neulet.2005.09.065
  8. Alp, H., Aytekin, I., Hatipoglu, N. K., Alp, A. and Ogun, M. : Effects of sulforophane and curcumin on oxidative stress created by acute malathion toxicity in rats. Eur. Rev. Med. Pharmacol. Sci. 16, 144 (2012).
  9. Hong, Y., Yan, W., Chen, S., Sun, C. R. and Zhang, J. M. : The role of Nrf2 signaling in the regulation of antioxidants and detoxifying enzymes after traumatic brain injury in rats and mice. Acta pharmacologica Sinica 31, 1421 (2010). https://doi.org/10.1038/aps.2010.101
  10. Innamorato, N. G., Rojo, A. I., Garcia-Yague, A. J., Yamamoto, M., de Ceballos, M. L. and Cuadrado, A. : The transcription factor Nrf2 is a therapeutic target against brain inflammation. J. Immunol. 181, 680 (2008). https://doi.org/10.4049/jimmunol.181.1.680
  11. Vomhof-Dekrey, E. E. and Picklo, M. J., Sr. : The Nrf2- antioxidant response element pathway: a target for regulating energy metabolism. J. Nutr. Biochem. 23, 1201 (2012). https://doi.org/10.1016/j.jnutbio.2012.03.005
  12. Somlyo, A. P. and Somlyo, A. V. : Signal transduction and regulation in smooth muscle. Nature 372, 231 (1994). https://doi.org/10.1038/372231a0
  13. Somlyo, A. P. and Somlyo, A. V. : From pharmacomechanical coupling to G-proteins and myosin phosphatase. Acta. Physiol. Scand. 164, 437 (1998). https://doi.org/10.1046/j.1365-201X.1998.00454.x
  14. Uehata, M., Ishizaki, T., Satoh, H., Ono, T., Kawahara, T., Morishita, T., Tamakawa, H., Yamagami, K., Inui, J., Maekawa, M. and Narumiya, S. : Calcium sensitization of smooth muscle mediated by a Rho-associated protein kinase in hypertension. Nature 389, 990 (1997). https://doi.org/10.1038/40187
  15. Sakurada, S., Takuwa, N., Sugimoto, N., Wang, Y., Seto, M., Sasaki, Y. and Takuwa, Y. : $Ca^{2+}$-dependent activation of Rho and Rho-kinase in membrane depolarization-induced and receptor stimulation-induced vascular smooth muscle contraction. Circ. Res. 93, 548 (2003). https://doi.org/10.1161/01.RES.0000090998.08629.60
  16. Kitazawa, T., Masuo, M. and Somlyo, A. P. : Protein-mediated inhibition of myosin light-chain phosphatase in vascular smooth muscle. Proc. Natl. Acad. Sci. USA 88, 9307 (1991). https://doi.org/10.1073/pnas.88.20.9307
  17. Gohla, A., Schultz, G. and Offermanns, S. : Roles for G(12)/ G(13) in agonist-induced vascular smooth muscle cell contraction. Circ. Res. 87, 221 (2000). https://doi.org/10.1161/01.RES.87.3.221
  18. Leung, T., Manser, E., Tan, L. and Lim, L. : A novel serine/ threonine kinase binding the Ras-related RhoA GTPase which translocates the kinase to peripheral membranes. J. Biol. Chem. 270, 29051 (1995). https://doi.org/10.1074/jbc.270.49.29051
  19. Matsui, T., Amano, M., Yamamoto, T., Chihara, K., Nakafuku, M., Ito, M., Nakano, T., Okawa, K., Iwamatsu, A. and Kaibuchi, K. : Rho-associated kinase, a novel serine/threonine kinase, as a putative target for small GTP binding protein Rho. EMBO. J. 15, 2208 (1996).
  20. Wier, W. G. and Morgan, K. G. : Alpha1-adrenergic signaling mechanisms in contraction of resistance arteries. Rev. Physiol. Biochem. Pharmacol. 150, 91 (2003).
  21. Jeon, S. B., Jin, F., Kim, J. I., Kim, S. H., Suk, K., Chae, S. C., Jun, J. E., Park, W. H. and Kim, I. K. : A role for Rho kinase in vascular contraction evoked by sodium fluoride. Biochem. Biophys. Res. Commun. 343, 27 (2006). https://doi.org/10.1016/j.bbrc.2006.02.120
  22. Wilson, D. P., Susnjar. M., Kiss, E., Sutherland, C. and Walsh, M. P. : Thromboxane A2-induced contraction of rat caudal arterial smooth muscle involves activation of $Ca^{2+}$ entry and $Ca^{2+}$ sensitization: Rho-associated kinase-mediated phosphorylation of MYPT1 at Thr-855, but not Thr-697. Biochem. J. 389, 763 (2005). https://doi.org/10.1042/BJ20050237
  23. Bhattacharya, B. and Roberts, R. E. : Enhancement of alpha2- adrenoceptor-mediated vasoconstriction by the thromboxanemimetic U46619 in the porcine isolated ear artery: role of the ERK-MAP kinase signal transduction cascade. Br. J. Pharmacol. 139, 156 (2003). https://doi.org/10.1038/sj.bjp.0705208
  24. Eylen, D. V., Oey, I., Hendrickx, M. and Loey, A. V. : Kinetics of the stability of broccoli (Brassica oleracea cv. italica) myrosinase and isothiocyanates in broccoli juice during pressure/ temperature treatments. J. Agric. Food Chem. 55, 2163 (2007). https://doi.org/10.1021/jf062630b