Antioxidants ofnew compounds from marine Algae prevent celldeath of endothelial cells


초록

Cytosolic oxidation by 4-hydroxy-2-nonenal (4HNE) and tert-butyl hydroperoxide (t-BHP) results in cell death of bovine aortic endothelial cells (BAEC). In this study, we have investigated the roles of antioxidants such as 2,3,6-tribromo-4,5-dihydroxy benzyl methyl ether (TDB) and phloroglucinol in preventing cell death. After treatment with oxidants for 6h, cells became compact and showed nuclear condensation, which were characteristics of early apoptosis. After l2h treatment, morphologic features including severe cytoplasm condensation, membrane blebbing, and apoptotic bodies were prominent and these findings were interpreted as characteristics of late-apoptosis. When the apoptotic cells were treated with antioxidants for 12h, both early and late apoptotic cells did show no significant change. After oxidant treated cells were incubated with antioxidant for 24h, the characteristics of early-apoptosis were eliminated but cells in lateapoptosis could not return to normal cells. These results suggest that TDB and phloroglucinol prevent the cells from dying through apoptosis induced by 4HNE and t-BHP in early stage.

키워드

참고문헌

  1. Bankson, D.D., Kestin, M. and Rifai N. : Role of free radicals in cancer and atherosclerosis. Clin. Lab. Med., 13 : 463-480, 1993
  2. Benedetti, A, Casini, AF., Ferrali, M. and Comporti M. : Effects of diffusible products of peroxidation of rat liver microsomal lipids. Biochem. J., 180: 303-312,1979 https://doi.org/10.1042/bj1800303
  3. Benedetti, A, Comporti, M. and Esterbauer, H. : Identification of 4-hydroxynonenal as a cytotoxic product originating from the peroxidation of liver microsomal lipids. Biochim. Biophys. Acta., 620 : 281-296,1980 https://doi.org/10.1016/0005-2760(80)90209-X
  4. Benedetti, A and Comporti, M. : Formation, reaction and toxicity of aldehydes produced in the course of lipid peroxidation in cellular membranes. Bioelectrochem. Bioenery, 18 :187-202, 1987 https://doi.org/10.1016/0302-4598(87)85021-3
  5. Esterbauer, H., Schaur, RJ. and Zollner, H. : Chemistry and Biochemistry of 4-hydroxynonenal, malonaldehyde, and related aldehyde. Free Radic. Bio. Med., 11 : 81-128,1991 https://doi.org/10.1016/0891-5849(91)90192-6
  6. Foresti, R., Sarathchandra, P., C1ark, J.E., Green, C.J. and Motterlini, R. : Peroxynitrite induces haem oxygenase-1 in vascular endothelial cells : a link to apoptosis. Biochem. J., 339: 729-736,1999 https://doi.org/10.1042/0264-6021:3390729
  7. Forman, H., Dorio, R.J. and Skelton, D.C. : Hydroperoxide-induced damage to alveolar macrophage function and membrane integrity. Arch. Biochem. Biophys., 259: 457-462, 1987 https://doi.org/10.1016/0003-9861(87)90512-1
  8. Forrest, V.J., Kang, Y.H., McClain, D.E., Robinson, D.H. and Ramakrishnan, N. : Oxidative stress-induced apoptosis prevented by trolox. Free Radical Biol. Med., 16 : 675684,1994
  9. Fraga, C.G. and Tappel, A. L. : Damage to DNA concurrent with lipid peroxidation in rat liver slices. Biochem. J., 252 : 893-898, 1988 https://doi.org/10.1042/bj2520893
  10. Hahn, S.M., Krishna, C.M. and Mitchell, J.B. : New directions for free radical cancer research and medical applications. Adv. Exp. Med. Biol., 366: 241-251,1994
  11. Kerr, J.E, Wyllie, A.H. and Currie, A.R : Apoptosis : A basis biological phenomenon with wide-ranging implications in tissue kinetics. Br. J. Cancer, 26: 239-257,1972 https://doi.org/10.1038/bjc.1972.33
  12. Kim, Y.K.,Ko, S.H., Woo, J.S., Lee, S.H. and Jung J.S. : Difference in H10l toxicity between intact renal tubules and cultured proximal tubular cells. Biochem. Pharmacol., 56 :489-495,1998 https://doi.org/10.1016/S0006-2952(98)00186-5
  13. Li, L., Hamilton Jr., R.F, Kirichenko, A. and Holian, A. : 4-hydroxynonenal-induced cell death in murine alveolar macrophages. oxicol. applied pharmacol., 139 : 135-143, 1996 https://doi.org/10.1006/taap.1996.0152
  14. Lovell, M.A, Ehmann, W.D., Mattson, M.P. and Markesbery, W.R. : Elevated 4-hydroxynonenal in VentricularFluid in Alzheimer's Disease. Neurobiol. Aging, 18 : 457-461,1997 https://doi.org/10.1016/S0197-4580(97)00108-5
  15. Mark, R.J, Lovell, M.A., Markesbery, W.R, Uchida, K. and Mattson, M.P. : A role for 4hydroxynonenal in disruption of ion homeostasis and neuronal death induced by amyloid $\beta$-peptide. J. Neurochem., 68 : 255-264,1997 https://doi.org/10.1046/j.1471-4159.1997.68010255.x
  16. Nagata, S. : Minireview Apoptotic DNA fragmentation. Experi. Cell res., 256 : 12-18, 2000 https://doi.org/10.1006/excr.2000.4834
  17. Park, H.J., Chung, H.Y., Kim, J. and Choi, J.S. : Antioxidant activity of 2,3,6-tribromo-4,5dihydroxy benzyl methyl ether from Symphyocladia latiuscula. J. Fish. Sci. Tech., 2(1): 1-7, 1999
  18. Riley, P.A : Free radicals in biology : oxidative stress and the effects of ionizing radiation. Int. J. Radiat. Biol.,65: 27-33, 1994 https://doi.org/10.1080/09553009414550041
  19. Sandoval, M., Zhang, X.J., Liu, X, Mannick, E.E., Clark, D.A. and Miller, M.J. : Peroxynitriteinduced apoptosis in T84 and raw 264.7 cells : attenuation by L-ascorbic acid. Free Rad. BioI. Med., 22(3): 489-495,1997 https://doi.org/10.1016/S0891-5849(96)00374-7
  20. Warren, M.C., Bump, E.A, Mediros, D. and Braunhut, S.J. : Oxidative stress-induced apoptosis of endothelial cells. Free Rad. Biol. ed., 29 : 537-547, 2000 https://doi.org/10.1016/S0891-5849(00)00353-1
  21. Wyllie, A.H., Kerr, J.F.R. and Currie, A.R : Cell death : The significance of apoptosis. Int. Rev. Cytol., 68: 251-306,1980 https://doi.org/10.1016/S0074-7696(08)62312-8