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Parathyroid hormone co-stimulation of hepatocyte proliferation is sensitive to protein kinase A and calcium channel inhibitors

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Abstract

Parathyroid hormone (PTH) mobilises calcium in the hepatocyte, an effect which is abolished by verapamil and staurosporine. In our study parathyroid hormone was shown to act additively to dHGF in inducing hepatocyte DNA synthesis. It is also shown that PTH induced the production of inositol 1,4,5 trisphosphate (IP3) andc-fos expression at early times in culture. Co-incubation of PTH and dHGF with ac-fos antisense oligodeoxynucleotide inhibited hepatocyte DNA synthesis, indicating that the additive effect of PTH is correlated with the induction ofc-fos. H-89, a PKA specific inhibitor, inhibited the PTH effect on IP3 production as well as the PTH effect on hepatocyte DNA synthesis. Verapamil and staurosporine also inhibited the PTH effect in dHGF-induced DNA synthesis. Therefore it is suggested that PKA mediated at a great extent the co-stimulatory effects of PTH on hepatocyte proliferation via IP3 production.

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References

  1. Chausmer, A. B., Sherman, S. S. and Wallach, S. (1972)Endocrinol 90:663–672.

    Google Scholar 

  2. Rixon, R. H., Isaacs, R. J. and Whitfield, J. F. (1989)J Cell Physiol 139:354–360.

    PubMed  Google Scholar 

  3. Klin, M., Smogorzewski, M., Khilnani, H., Michnowska, M. and Massry, S. G. (1994)Am J Physiol 267:G754-G763.

    PubMed  Google Scholar 

  4. Kano, J., Sugimoto, T., Kanatani, M., Kuroki, Y., Tsukamoto, T., Fukase, M. and Chihara, K. (1994)J Cell Physiol 161:358–366.

    PubMed  Google Scholar 

  5. Cohen, P. (1988)Proc. R. Soc. London B234:115–144.

    Google Scholar 

  6. Michalopoulos, G. K. (1990)FASEB J. 4:176–187.

    PubMed  Google Scholar 

  7. Fausto, N. and Webber, E. M. (1993)Crit. Rev. Eukaryot. Gene Expr. 3:117–135.

    PubMed  Google Scholar 

  8. Etienne, P. L., Baffet, G., Desvergenes, B., Boisnard-Rissel, M., Glaise, D. and Guguen-Guillouzo, C. (1988)Oncogene Res. 3:255–262.

    PubMed  Google Scholar 

  9. Michalopoulos, G. K. (1994) HGF and Liver Growth Regulation in: “Liver Carcinogenesis: The Molecular Pathways”. G. G. Skouteris (ed.), Springer Verlag H88, pp. 13–32.

  10. Sikorska, M., Whitfield, J. F. and Rixon, R. H. (1983)J Cell Physiol 115:297–304.

    PubMed  Google Scholar 

  11. Mine, T., Kojima, I. and Ogata, E. (1989)Biochem. J. 258:889–894.

    PubMed  Google Scholar 

  12. Seglen, O. O. (1976)Meth. Cell Biol. 13:29–83.

    Google Scholar 

  13. Skouteris, G. G. and McMenamin, M. (1992)Biochem. J. 281:729–733.

    PubMed  Google Scholar 

  14. Kapp, L. N., Brown, S. L. and Levecz, R. R. (1974)Biochim. Biophys. Acta 361:140–143.

    PubMed  Google Scholar 

  15. Chomczynski, P. and Sacchi, N. (1987)Anal. Biochem. 162:156–159.

    PubMed  Google Scholar 

  16. Shima, N., Tsuda, E., Goto, M., Yano, K., Hayasaka, H. and Higashio, K. (1994)Biochem. Biophys. Res. Commun. 200:808–815.

    PubMed  Google Scholar 

  17. Kruijer, W., Skelly, H., Botteri, F., Van der Putten, H., Barber, J. R., Verma, I. M. and Leffert, H. L. (1986)J. Biol. Chem. 260:7929–7933.

    Google Scholar 

  18. Fabregat, I., Dejuan, C., Nakamura, T. and Benito, M. (1992)Biochem. Biophys. Res. Commun. 189:684–690.

    PubMed  Google Scholar 

  19. Skouteris, G. G. and Kaser, M. R. (1992)J Cell Physiol 150:353–359.

    PubMed  Google Scholar 

  20. Skouteris, G. G. and Schröder, C. H. (1995)Biochem. J., in press.

  21. Abdul-Badi, A., Jueppner, H., Westerberg, D., Potts, J. T. and Segre, G. V. (1989)Endocrinol. 124:1107–1113.

    Google Scholar 

  22. Tamure, T., Sakamoto, H. and Filburn, C. R. (1989)Biochem. Biophys. Res. Commun. 159:1352–1358.

    PubMed  Google Scholar 

  23. Stojceva-Taneva, O., Fadda, G. Z., Smogorzewski, M. and Massry, S. G. (1993)Nephron 64:592–599.

    PubMed  Google Scholar 

  24. Skouteris, G. G. and Kaser, M. R. (1991)Biochem. Biophys. Res. Commun. 178:1240–1246.

    PubMed  Google Scholar 

  25. Osada, S., Nakashima, S., Saji, S., Nakamura, T. and Nozawa, Y. (1992)FEBS Lett. 297:271–274.

    PubMed  Google Scholar 

  26. Zuscik, M. J., Puzas, J. E., Rosier, R. N., Gunter, K. K. and Gunter, T. E. (1994)Arch. Biochem. Biophys. 315:352–361.

    PubMed  Google Scholar 

  27. Ohtsuki, M. and Massague, J. (1992)Mol. Cell Biol. 12:261–265.

    PubMed  Google Scholar 

  28. Klin, M., Smogorzewski, M., Khilnani, H., Michnowska, M. and Massry, S. G. (1994)Am. J. Physiol. 267:G754–763.

    PubMed  Google Scholar 

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Skouteris, G.G. Parathyroid hormone co-stimulation of hepatocyte proliferation is sensitive to protein kinase A and calcium channel inhibitors. Biosci Rep 16, 343–350 (1996). https://doi.org/10.1007/BF01855017

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  • DOI: https://doi.org/10.1007/BF01855017

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