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Molecular basis of α-tocopherol inhibition of smooth muscle cell proliferation in vitro

  • Daniel Boscoboinik
  • Eric Chatelain
  • Gianna-M. Bartoli
  • Angelo Azzi
Part of the EXS book series (EXS, volume 62)

Summary

The molecular events responsible for the inhibition of cell proliferation by α-tocopherol have been investigated. Smooth muscle cells in vitro have been shown to be specifically inhibited by α-tocopherol with a concomitant inhibition of protein kinase C activity.β-Tocopherol was inactive, despite its similar radical scavenging activity. The point of inhibition of α-tocopherol relative to the cell cycle was localized in the late G1 phase. A second effect of α-tocopherol observed with smooth muscle cells was the stimulation of protein kinase C biosynthesis in both the S and G2 phases of the cell cycle. The implications of these findings for the onset of arteriosclerosis are discussed.

Keywords

Smooth Muscle Cell Vascular Smooth Muscle Cell Smooth Muscle Cell Proliferation Arterial Smooth Muscle Cell Liquid Scintillation Analyzer 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations

FCS

fetal calf serum

HU

hydroxyurea

PDBu

phorbol dibutyrate

PDGF

plateletderived growth factor

PKC

protein kinase C

VSMC

vascular smooth muscle cells.

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References

  1. Adams, J. C., and Gullick, W. J. (1989) Differences in phorbol ester-induced down-regulation of protein kinase C between cell lines. Biochem. J. 257: 905–911.PubMedGoogle Scholar
  2. Alexander, D. R., Hexham, J. M., Lucas, S. C., Graves, J. D., Cantrell, D. A., and Crumpton, M. J. (1989) A protein kinase C pseudosubstrate peptide inhibits phosphorylation of the CDS antigen in streptolysin-O permeabilized human T lymphocytes. Biochem. J. 260: 893–901.PubMedGoogle Scholar
  3. Ashihara, T., and Baserga, R. (1979) Cell Synchronization. Methods Enzym. 58: 248–262. (eds Jakoby and Pastan).CrossRefGoogle Scholar
  4. Bobik, A., Grooms, A., Miller, J. A., Mitchell, A., and Grinpukel, S. (1990) Growth factor activity of endothelin on vascular smooth muscle. Am. J. Physiol. 258: C408-C415.Google Scholar
  5. Boscoboinik, D., Szewczyk, A., Hensey, C., and Azzi, A. (1991) Inhibition of cell proliferation by a-tocopherol. Role of protein kinase C. J. Biol. Chem. 266: 6188–6194.Google Scholar
  6. Bunyan, J., McHale, D., Green, J., and Marcinkewicz, S. (1961) Brit. J. Nutr. 15: 253–257.PubMedCrossRefGoogle Scholar
  7. Burlakova, E. B., Kukhtina, E. N., Olkhovskaya, L P., Sarycheva, L K., Sinkina, E. B., and Khrapova, N. G. (1980) Biophysics 24: 989–993.Google Scholar
  8. Burton, G. W., and Ingold, K. U. (1981) J. Amer. Chem. Soc. 103: 6472–6477.CrossRefGoogle Scholar
  9. Campisi, J. E., Medrano, E., Morreo, G., and Pardee, A. B. (1982) Restriction point control of cell growth by a labile protein: evidence for increased stability in transformed cells. Proc. Natl. Acad. Sci USA 79: 436–440.PubMedCrossRefGoogle Scholar
  10. Castellot, J. J., Pukac, L. A., Caleb, B. L., Wright, T. C., and Karnovsky, M. J. (1989) Heparin selectively inhibits a protein kinase C-dependent mechanism of cell cycle progression in calf aortic smooth muscle cells. J. Cell. Biol. 109: 3147–3155PubMedCrossRefGoogle Scholar
  11. Desgranges, C., Campan, M., Gadeau, A-P, Geurineau, N., Mollard, P., and Razaka, G. (1991) Influence of 8-(N,N-diethylaniino) octyl-3,4,5-trimethoxybenzoate (TMB-8) on cell cycle progression and proliferation of cultured arterial smooth muscle cells. Biochem. Pharm. 41: 1045–1054.PubMedCrossRefGoogle Scholar
  12. Egan, R. W., Gale, P. H., and Kuehl, F. A. (1979) Reduction of hydroperoxides in the prostaglandin biosynthesis pathway by a microsomal peroxidase. J. Biol. Chem. 254: 3295–3302.PubMedGoogle Scholar
  13. Egan, R. W., Gale, P. H., and Kuehl, F. A. (1979) G, events and regulation of cell proliferation. Science 246: 603–608.Google Scholar
  14. Geisterfer, A. A., Peach, M. J., and Owens, G. K. (1988) Angiotensin II induces hypertrophy, not hyperplasia, of cultured rat aortic smooth muscle cells. Circ. Res. 62: 749–756.PubMedGoogle Scholar
  15. Gospodarowicz, D., Moran, J. S., and Braun, D. L. (1977) Control of proliferation of bovine vascular endothelial cells. J. Cell. Physiol. 91: 377–385.PubMedCrossRefGoogle Scholar
  16. Griendling, K. K., Tsuda, T., and Alexander, R. W. (1989) Endothelian stimulates diacylglycerol accumulation and activates protein kinase C in cultured vascular smooth muscle cells. J. Biol. Chem. 264: 8237–8240.PubMedGoogle Scholar
  17. Kllne, K., Cochran, G. S., and Sanders, B. G. (1990) Growth-inhibitory effects of vitamin E succinate on retrovirus-transformed tumor cells in vitro. Nutr. Cancer 14: 27–41.CrossRefGoogle Scholar
  18. Kraft, A. S., and Anderson, W. B. (1983) Phorbol esters increase the amount of phosphoUpid-dependent protein kinase, associated with plasma membrane. Nature 301: 621–623.PubMedCrossRefGoogle Scholar
  19. Ku, G., Doherty, N. S., Wolos, J. A., and Jackson, R. L. (1988) Inhibition by probucol of interleukin-1 secretion and its implication in atherosclerosis. Am. J. Cardiol. 62: 77B.CrossRefGoogle Scholar
  20. Lang, J. K., Gohil, K., and Packer, L. (1986) Simultaneous determination of tocopherols, ubiquinols, and ubiquinones in blood, plasma, tissue homogenates, and subcellular fractions. Anal. Biochem. 157: 106–116.PubMedCrossRefGoogle Scholar
  21. Loesberg, C., van Wijk, R., Zandbergen, J., van Aken, W. G., van Mourik, J. A., and de Groot, Ph. G. (1985) Cell cycle-dependent inhibition of human vascular smooth muscle cell proliferation by prostaglandin El. Exp. Cell Res. 160: 117–125.PubMedCrossRefGoogle Scholar
  22. Matsumoto, H., and Sasaki, Y. (1989) Staurosporine, a protein kinase C inhibitor, interferes with proliferation of arterial smooth muscle cells. Biochem. Biophys. Res. Commun. 158: 105–109.PubMedCrossRefGoogle Scholar
  23. Mukai, K., Fukuda, K., and Ishizu, K. (1988) Stopped-flow investigation of antioxidant activity of tocopherols. Finding of new tocopherol derivatives having higher antioxidant activity than a-tocopherol. Chem. Phys. Lipids 46: 31–36.PubMedCrossRefGoogle Scholar
  24. Munro, J. M., and Cochran, R. S. (1988) The pathogenesis of atherosclerosis: Atherogenesis and Inflammation. Lab Invest. 58: 249–261.PubMedGoogle Scholar
  25. Niki, E., Tsuchiya, J., Yoshikawa, Y., Yamamoto, Y., and Kamiya, Y. (1987) Bull. Chem. Soc. Jpn. 60: 2161–2165.Google Scholar
  26. Owens, G. K. and Reidy, M. A. (1985) Hyperplastic growth response of vascular smooth muscle cells following induction of acute hypertension in rats by aortic coarctation. Circ. Res. 57: 695–705.PubMedGoogle Scholar
  27. Packer, L., and Landvik, S. (1989) Vitamin E: Introduction to biochemistry and health benefits. Ann. NY Acad. Sci 570: 1–6.PubMedCrossRefGoogle Scholar
  28. Parker, P. J., Kour, G., Marais, R. M., Mitchell, F., Pears, C., Schaap, D., Stabel, S., and Webster, C. (1989) Protein kinase C - a family aff’air. Mol. Cell. Endocrinol. 65: 1–11.PubMedCrossRefGoogle Scholar
  29. Prasad, K. N., and Edwards-Prasad, J. (1982) Effects of tocopherol (vitamin E) acid succinate on morphological alterations and growth inhibition in melanoma cells in culture. Cancer Res. 42: 550–555.PubMedGoogle Scholar
  30. Raines, E. W., Dower, S. K., and Ross, R. (1989) Interleukin-1 mitogenic activity for fibroblasts and smooth muscle cells was due to PDGF-AA. Science 243: 393.PubMedCrossRefGoogle Scholar
  31. Ran, W., Dean, M., Levine, R. A., Henckle, C., and Campisi, J. (1986) Induction of c-fos and c-myc mRNA by epidermal growth on calcium ionophore is cAMP dependent. Proc. Natl. Acad. Sci. USA 83: 8216–8220.PubMedCrossRefGoogle Scholar
  32. Ross, R. (1986) The pathogenesis of atherosclerosis - An update. N. Engl. J. Med. 314: 488–500.PubMedCrossRefGoogle Scholar
  33. Ross, R., Glomset, J. A., Kariya, B., and Harker, L. (1974) A platelet-dependent serum factor that stimulates the proliferation of arterial smooth muscle cells in vitro. Proc. Natl. Acad. Sci. USA 71: 1207–1210.PubMedCrossRefGoogle Scholar
  34. Rozengurt, E. (1986) Early signals in the mitogenic response. Science 234: 161–166.PubMedCrossRefGoogle Scholar
  35. Schwartz, S. M., Campbell, G. R., and Campbell, J. H. (1986) Replication of smooth muscle cells in vascular disease. Circ. Res. 58: 427–444.PubMedGoogle Scholar
  36. Slack, R., and Proulx, P. (1989) Studies on the effects of vitamin E on neuroblastoma NIE 115. Nutr. Cancer 12: 75–82.PubMedCrossRefGoogle Scholar
  37. Tappel, A. L. (1972) Vitamin E and free radical peroxidation of hpids. Ann. NY Acad. Sci. 203: 12–27.PubMedCrossRefGoogle Scholar
  38. Thyberg, J., and Palmberg, L. (1987) The calcium antagonist nisoldipine and the calmodulin antagonist W-7 synergistically inhibit initiation of DNA synthesis in cultured arterial smooth muscle cells. Biol Cell 60: 125–132.PubMedCrossRefGoogle Scholar
  39. Trihvas, I., and Brown, J. H. (1989) Increases in intracellular Ca regulate the binding of [H]phorbol 12,13-dibutyrate to intact 132N1 astrocytoma cells. J. Biol. Chem. 264: 3102–3107.Google Scholar
  40. Urano, S., Yano, K., and Matsuo, M. (1988) Membrane stabilizing effect of vitamin E: effect of a-tocopherol and its model compounds on fluidity of lecithin Uposomes. Biochem. Biophys. Res. Commun. 150: 469–475.PubMedCrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag Basel/Switzerland 1992

Authors and Affiliations

  • Daniel Boscoboinik
    • 1
  • Eric Chatelain
    • 1
  • Gianna-M. Bartoli
    • 1
  • Angelo Azzi
    • 1
  1. 1.Institut für Biochemie und MolekularbiologieUniversität BernBernSwitzerland

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