1887

Abstract

Rat pheochromocytoma PC12 cells were permanently transfected with a plasmid vector, containing the gene of human immunodeficiency virus type 1 (HIV-1). Various clones were obtained showing the production of different levels of bioactive Tat protein (Tat) after transient contransfection with an HIV-1 long terminal repeat-chloramphenicol acetyltransferase reporter plasmid. Under conditions of serum starvation, -positive PC12 clones expressing high levels of Tat showed a significantly ( < 0.05) higher proliferation rate with respect to both mock-transfected PC12 cells and -positive PC12 cells expressing lower levels of Tat. Moreover, all -positive PC12 cell clones showed a partial morphological differentiation into sympathetic-like neurons, when seeded in low density (5 × 10 cells/cm) cultures. On the other hand, mock-transfected PC12 cells showed the round shaped morphology typical of untreated PC12 cells and displayed signs of neuronal differentiation only after treatment with 100 ng/ml of nerve growth factor. The addition of 5 µg/ml of anti-Tat monoclonal antibody to the culture medium of -positive PC12 cell clones almost completely blocked their increased proliferation rate ( < 0.05), but did not affect neuronal differentiation. A significant ( < 0.05) increase in cell proliferation was consistently observed in PC12 cells supplemented with low concentrations of Tat (5 to 25 ng/ml), whereas neuronal differentiation was hardly affected by exogenous Tat. Our data strongly suggest that Tat exerts a complex influence on the proliferation and differentiation of PC12 cells, and this might help in increasing understanding of the pathogenesis of the frequent neurological disorders observed in AIDS patients.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-74-12-2587
1993-12-01
2024-04-25
Loading full text...

Full text loading...

/deliver/fulltext/jgv/74/12/JV0740122587.html?itemId=/content/journal/jgv/10.1099/0022-1317-74-12-2587&mimeType=html&fmt=ahah

References

  1. Brenneman D. E., Westbrook G. L., Fitzgerald S. P., Ennist D. L., Elkins K. L., Ruff M. R., Pert C. B. 1988; Neuronal cell killing by the envelope protein of HIV and its prevention by vasoactive intestinal peptide. Nature, London 335:639–642
    [Google Scholar]
  2. Buonaguro L., Barillari G., Chang H. K., Bohan C. A., Kao V., Morgan R., Gallo R. C., Ensoli B. 1992; Effects of the human immunodeficiency virus type 1 tat protein on the expression of inflammatory cytokines. Journal of Virology 66:7159–7167
    [Google Scholar]
  3. Cullen B. R. 1986; Trans-activation of human immunodeficiency virus occurs via a bimodal mechanism. Cell 46:973–982
    [Google Scholar]
  4. Ensoli B., Barillari G., Zaki Salahuddin S., Gallo R. C., Wong-Staal F. 1990; Tat protein of HIV-1 stimulates growth of cells derived from Kaposi’s sarcoma lesions of AIDS patients. Nature, London 345:84–86
    [Google Scholar]
  5. Ensoli B., Buonaguro L., Barillari G., Fiorelli V., Gendelman R., Morgan R. A., Wingfield P., Gallo R. C. 1993; Release, uptake and effects of extracellular human immunodeficiency virus type 1 tat protein on cell growth and viral transactivation. Journal of Virology 67:277–287
    [Google Scholar]
  6. Frankel A. D., Pabo C. O. 1988; Cellular uptake of the Tat protein from human immunodeficiency virus. Cell 55:1189–1193
    [Google Scholar]
  7. Gorman C. M., Moffat L. F., Howard B. H. 1982; Recombinant genomes which express chloramphenicol acetyltransferase in mammalian cells. Molecular and Cellular Biology 2:1044–1051
    [Google Scholar]
  8. Greene L. A. 1978; Nerve growth factor prevents the death and stimulates neuronal differentiation of clonal PC12 pheochromo-cytoma cells in serum-free medium. Journal of Cell Biology 78:747–755
    [Google Scholar]
  9. Greene L. A., Tischler A. S. 1976; Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. Proceedings of the National Academy of Sciences, U,. S,. A 73:2424–2428
    [Google Scholar]
  10. Grossi M. P., Caputo A., Rimessi P., Chiccoli L., Balboni P. G., Barbanti-Brodano G. 1988; New BK virus episomal vector for complementary DNA expression in human cells. Archives of Virology 102:275–283
    [Google Scholar]
  11. Huff K. R., Guroff G. 1979; Nerve growth factor-induced reduction in epidermal growth factor responsiveness and epidermal growth factor receptors in PC12 cells: an aspect of cell differentiation. Biochemical and Biophysical Research Communications 89:175–180
    [Google Scholar]
  12. Kim S. J., Winokur T. S., Lee H. D., Danielpour D., Kim K. Y., Geiser A. G., Chen L. S., Sporn M. B., Roberts A. B., Jay G. 1991; Overexpression of transforming growth factor-beta in transgenic mice carrying the human T-cell lymphotropic virus type I tax gene. Molecular and Cellular Biology 11:5222–5228
    [Google Scholar]
  13. Martelli A. M., Neri L. M., Gilmour R. S., Barker P. J., Huskisson N. S., Manzoli F. A., Cocco L. 1991; Temporal changes in intracellular distribution of protein kinase C in Swiss 3T3 cells during mitogenic stimulation with insulin-like growth factor I and bombesin: translocation to the nucleus follows rapid changes in nuclear polyphosphoinositides. Biochemical and Biophysical Research Communications 177:480–487
    [Google Scholar]
  14. Merrill J. E., Chen I. S. Y. 1991; HIV-1, macrophages, glial cells, and cytokines in AIDS nervous system disease. FASEB Journal 5:2391–2397
    [Google Scholar]
  15. Neri L. M., Mazzotti G., Capitani S., Maraldi N. M., Cinti C., Baldini N., Rana R., Martelli A. M. 1992; Nuclear matrix bound replicational sites detected in situ by 5-bromodeoxyuridine. Histochemistry 98:19–32
    [Google Scholar]
  16. Prince R. W., Brew B. J., Sidtis J. J., Rosenblum M., Scheck A. C., Cleary P. 1988; The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586–592
    [Google Scholar]
  17. Rezai A., Martinez-Maza O., Gaynor R., Kishimoto T., Hirano T., Mitsuyasu R. T., Miles S. A. 1991; HIV-tat increases IL-6 production by and proliferation of AIDS-KS derived cells. Proceedings of the Annual Meeting of the American Society of Clinical Oncology 10:A6
    [Google Scholar]
  18. Rosen C. A., Sodroski J. C., Haseltine W. A. 1985; The location of cis-acting regulatory sequences in the human T cell lymphotropic virus type III (HTLV-III/LAV) long terminal repeat. Cell 41:813–823
    [Google Scholar]
  19. Rosen C. A., Sodroski J. G., Goh W. C., Dayton A. I., Lippke J., Haseltine W. A. 1986; Post-transcriptional regulation accounts for the trans-activation of human T-lymphotropic virus type III. Nature, London 319:555–559
    [Google Scholar]
  20. Rudkin B. B., Lazarovici P., Levi B. Z., Abe Y., Fuiita K., Guroff G. 1989; Cell cycle-specific action of nerve growth factor in PC12 cells: differentiation without proliferation. EMBO Journal 241:3319–3325
    [Google Scholar]
  21. Rydel R. E., Greene L. A. 1987; Acid and basic fibroblast growth factors promote stable neurite outgrowth and neuronal differentiation in cultures of PC12 cells. Journal of Neuroscience 7:3639–3653
    [Google Scholar]
  22. Sastry K. J., Reddy H. R., Pandita R., Tolpal K., Aggarwal B. B. 1990; HIV-1 tat gene induces tumor necrosis factor-beta (lymphotoxin) in a human B-lymphoblastoid cell line. Journal of Biological Chemistry 265:20091–20093
    [Google Scholar]
  23. Satoh T., Nakamura S., Taga T., Matsuda T., Hirano T., Kishimoto T., Kaziro Y. 1988; Induction of neuronal differentiation in PC12 cells by B-cell stimulatory factor 2/interleukin 6. Molecular and Cellular Biology 8:3546–3549
    [Google Scholar]
  24. Taylor J. P., Cupp C., Diaz A., Chowdhury M., Khalili K., Jimenez S. A., Amini S. 1992; Activation of expression of genes coding for extracellular matrix proteins in tat-producing glioblastoma cells. Proceedings of the National Academy of Sciences U,. S,. A 89:9617–9621
    [Google Scholar]
  25. Viscidi R. P., Mayur K., Lederman H. M., Frankel A. D. 1989; Inhibition of antigen-induced lymphocyte proliferation by tat protein from HIV-1. Science 246:1606–1608
    [Google Scholar]
  26. Wahl S. M., Allen J. B., McCartney-Francis N., Morganti-Kossman M. C., Kossman T., Ellingsworth L., Mai U. E. H., Mergenhagen S. E., Orenstein J. M. 1991; Macrophage- and astrocyte-derived transforming growth factor β as a mediator of central nervous system dysfunction in acquired immune deficiency syndrome. Journal of Experimental Medicine 173:981–991
    [Google Scholar]
  27. Weiser B., Peress N., La Neve D., Eilbott D. J., Seidman R., Burger H. 1990; Human immunodeficiency virus type 1 expression in the central nervous system correlates directly with extent of disease. Proceedings of the National Academy of Sciences, U,. S,. A 87:3997–4001
    [Google Scholar]
  28. Wright C. M., Felber B. K., Paskalis H., Pavlakis G. N. 1986; Expression and characterization of the trans-activator of HTLV-III/LAV virus. Science 234:988–992
    [Google Scholar]
  29. Zauli G., Davis B. R., Re M. C., Visani G., Furlini G., LaPlaca M. 1992; Tat protein stimulates production of transforming growth factor-β 1 by marrow macrophages: a potential mechanism for HIV-1 induced hematopoietic suppression. Blood 80:3036–3043
    [Google Scholar]
  30. Zauli G., Furlini G., Re M. C., Milani D., Capitani S., La Placa M. 1993; Human immunodeficiency virus type 1 (HIV-1) tat-protein stimulates the production of interleukin-6 (IL-6) by peripheral blood monocytes. Microbiologica 16:115–120
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-74-12-2587
Loading
/content/journal/jgv/10.1099/0022-1317-74-12-2587
Loading

Data & Media loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error