Advertisement

The Receptor Binding of Insulin and Poly(Adpribose)-Synthesis during the Cell Cycle

  • H. Altmann
  • O. Török
  • P. Kovacs
  • G. Csaba
Chapter
Part of the Experimental Biology and Medicine book series (EBAM, volume 5)

Abstract

Hormones can influence the poly(ADP-ribose)-synthesis in the nuclei of cells. But ADP-ribosylation of a component of the receptor adenylate cyclase system influences also cell functions via the cAMP level. In our investigations Chang liver cells, which are target cells for insulin, and HeLa cells were treated with insulin, 3-methoxybenzamide or both agents together and the insulin receptor sites determined with FITC-labeled insulin. In HeLa cells insulin as well as methoxybenzamide decreased the FITC-insulin binding to cytoplasmic and nuclear receptor sites. In contrast to this result, both compounds generates higher receptor binding sites in Chang liver cells. Both cell lines were synchronized by thymidine and N20 treatment. HeLa cells had after pretreatment with insulin, especially during the S-phase, decreased insulin receptor sites. These investigations were done at different times after starting the cell cycle progression after the release of the mitotic block. The highest binding values were obtained at the end of the S-phase and beginning of G2. The poly(ADP-ribose)-synthesis in untreated HeLa cells showed 3 peaks. The first peak was at the beginning of G1, the second at the first part of the S-phase and the third near the end of the DNA synthesis. In insulin pretreated HeLa cells only the 1st and 2nd peak appeared, not the third. The poly(ADP-ribose)-synthesis in the 1st part of S-phase was strongly increased. In Chang liver cells, insulin pretreatment changes the PAR-synthesis pattern strongly. From nucleoid sedimentation studies we could show that poly(ADP-ribose)-synthesis on DNA-nuclear cage binding sites is reduced after insulin treatment, which is possibly connected to increased transcription activity.

Keywords

HeLa Cell Insulin Receptor Nuclear Envelope Insulin Stimulation Chang Liver Cell 
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.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Edmunds, L.N, K.J. Adama, 1981, Clocked cell cycle clocks. Science 211, 1002–1013.PubMedCrossRefGoogle Scholar
  2. 2.
    Katada, T., M. Ui, 1982, Direct modification of the membrane adenylate cyclase system by islet-activating protein due to ADP-ribosylation of a membrane protein. Proc.Natl.Acad.Sci.USA 79, 3129–3133.PubMedCrossRefGoogle Scholar
  3. 3.
    Tanigawa, Y., M. Tsuchiya, Y. Imai, M. Shimoyama, 1983, ADP-ribosylation regulates the phosphorylation of histones by the catalytic subunit of cyclic AMP dependent protein kinase. FEBS letters 160, 217–220.PubMedCrossRefGoogle Scholar
  4. 4.
    Wong, M., M. Miwa, T. Sugimura, S. Smulson, 1983, Relationship between histone H1 poly (adenosine diphosphate ribosylation) and H1 phosphorylation using anti-poly(adenosine diphosphate ribose) antibody. Biochemistry 22, 2384–2389.PubMedCrossRefGoogle Scholar
  5. 5.
    Roth, R.A., D.J. Cassell, 1983, Insulin receptor: Evidence that it is a protein kinase. Science 219, 299–301.PubMedCrossRefGoogle Scholar
  6. 6.
    INGEBRITSEN, T.S., P. COHEN, 1983, Protein phosphatase: Properties and role in cellular regulation. Science 221, 331–338.PubMedCrossRefGoogle Scholar
  7. 7.
    Hildebrandt, J.D., R.D. Sekura, J. Codina, R. Iyengar, Ch.R. Manclark, L. Birnbaumer, 1983, Stimulation and inhibition of adenyl cyclases mediated by distinct regulatory proteins. Nature 302, 706–709.PubMedCrossRefGoogle Scholar
  8. 8.
    Török, O., H. Altmann, 1982, The influence of insulin on poly(ADP-ribose)-synthese and the phases of the cell cycle. In: “DNA-Repair and Chromatin”. Proc.Symp.Saalfelden 1981. Eds.: H. Altmann, G. Klein. Seibersdorf Press, 15–20.Google Scholar
  9. 9.
    Seals, J.R., L. Jarett, 1980, Activation of pyruvate dehydrogenase by direct addition of insulin to an isolated plasma membrane/mitochondria mixture: Evidence for generation of insulin’s second messenger in a subcellular system. Proc.Natl.Acad.Sci.USA 77, 77–81.PubMedCrossRefGoogle Scholar
  10. 10.
    Beachy, J.C., D. Goldman, M.P. Czech, 1981, Lectins activate lymphocyte pyruvate dehydrogenase by a mechanism sensitive to protease inhibitors. Proc.Natl.Acad.Sci.USA 78, 6256–6260.PubMedCrossRefGoogle Scholar
  11. 11.
    van Oberghen, E., P.M. Spooner, C.R. Kahn, S.S. Chernick, M.M. Garrison, F.A. Karlsson, C. Grunfeld, 1979, Insulin-receptor antibodies mimic a late insulin effect. Nature 280, 500–502.CrossRefGoogle Scholar
  12. 12.
    Vigneri, R., I.D. Goldfine, K.Y. Wong, G.J. Smith, V. Pezzino, 1978, The nuclear Envelope. The major site of insulin binding in rat liver nuclei. J.Biol.Chem. 253, 2098–2103.PubMedGoogle Scholar
  13. 13.
    Horvat, A., E. Li, P.G. Katsoyannis, 1975, Cellular binding sites for insulin in rat liver. Biochim.et Biophys.Acta 382, 609–620.CrossRefGoogle Scholar
  14. 14.
    Slattery, E., J.D. Dignam, T. Matsui, R.G. Roeder, 1983, Purification and analysis of a factor which suppresses nick induced transcription by RNA polymerase II and its identity with poly(ADP-ribose)polymerase. J.Biol.Chem. 258, 5955–5959.PubMedGoogle Scholar
  15. 15.
    Purrello, F., R. Vigneri, G.A. Clawson, I.D. Goldfine, 1982, Insulin stimulation of nucleoside triphosphatase activity in isolated nuclear envelopes. Science 216, 1005–1007.PubMedCrossRefGoogle Scholar
  16. 16.
    Brkic, G., A. Topaloglou, H. Altmann, 1984, Poly(ADP-ribose) in nucleoids. OEFZS Ber.Nr. 4267, BL-450.Google Scholar
  17. 17.
    Rao, P.N., 1968, Mitotic synchrony in mammalian cells treated with nitrons oxide at high pressure. Science 160, 774–776.PubMedCrossRefGoogle Scholar
  18. 18.
    Altmann, H., I. Dolejs, 1982, Poly(ADP-ribose)synthesis, chromatin structure and DNA repair in cells of patients with different diseases. Progr.in Mut.Res. 4, 167–175.Google Scholar
  19. 19.
    Altmann, H., 1983, Poly(ADP-ribose)-Synthese and Regulationsstörungen bei Erkrankungen. Wr.klin.Wochenschr. 95, 861–864.Google Scholar
  20. 20.
    Altmann, H., 1983, Faktoren, die DNA-Reparaturprozesse innerhalb des Zellzyklus beeinflussen. Acta histochem. 27, 87–94.Google Scholar
  21. 21.
    Song, M.H., K.W. Adolph, 1983, ADP-ribosylation of nonhistone proteins during the HeLa cell cycle. Biochem.Biophys.Res.Comm. 115, 938–945.PubMedCrossRefGoogle Scholar

Copyright information

© The Humana Press Inc. 1984

Authors and Affiliations

  • H. Altmann
    • 1
  • O. Török
    • 2
  • P. Kovacs
    • 2
  • G. Csaba
    • 2
  1. 1.Institute of BiologyResearch Centre SeibersdorfSeibersdorfAustria
  2. 2.Department of BiologySemmelweis University of MedicineBudapestHungary

Personalised recommendations