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Bovine seminal RNase induces apoptosis in normal proliferating lymphocytes

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International Journal of Clinical and Laboratory Research

Abstract

Bovine seminal ribonuclease is a member of the RISBAses (ribonucleases with special biological actions) family. It exerts specific anti-tumor, embryotoxic, aspermatogenic and immunosuppressive activities. The cytotoxic effect of bovine seminal ribonuclease on tumor cells is accompanied by the induction of apoptosis. We provide ultrastructural and flow cytometry evidence of apoptotic death following bovine seminal ribonuclease treatment, in normal cells and phytohemagglutinin-stimulated lymphocytes. Transmission and scanning electron microscopy, which were fully supported by flow cytometry data, showed typical features of apoptosis, such as decreased cell size, chromatin condensation, fragmentation in micronuclei, and the presence of apoptotic bodies.

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References

  1. D’Alessio G, Parente A, Guida C, Leone E. Dimeric structure of seminal ribonuclease. FEBS Lett 1972; 27:285.

    Article  PubMed  CAS  Google Scholar 

  2. Blackburn, P, Moore S. Pancreatic ribonuclease. In: Boyer PD, ed. The enzymes, 3rd edn. New York: Academic Press, 1982.

    Google Scholar 

  3. Libonati M, Floridi A. Breakdown of double-stranded RNA by bull semen ribonuclease. Eur J Biochem 1969; 8:81.

    Article  PubMed  CAS  Google Scholar 

  4. Taniguchi T, Libonati M. Action of ribonuclease BS-1 on a DNA-RNA hybrid. Biochim Biophys Res Commun 1974; 58:280.

    Article  CAS  Google Scholar 

  5. Yakovlev G, Moiseyev GP, Sorrentino S, De Prisco R, Libonati M. Single-strand-preferring Rnases degrade doublestranded RNAs by destabilizing its secondary structure. J Biomol Struct Dyn 1997; 15:243.

    PubMed  CAS  Google Scholar 

  6. Tamburrini M, Scala G, Verde C, Ruocco MR, Parente A, Venuta S, D’Alessio G. Immunosuppressive activity of bovine seminal Rnase on T-cell proliferation. Eur J Biochem 1990; 190:145.

    Article  PubMed  CAS  Google Scholar 

  7. Piccoli R, Tamburrini M, Piccialli G, Di Donato A, Parente A, D’Alessio G. The dual-mode quaternary structure of seminal RNase. Proc Natl Acad Sci U S A 1992; 89:1870.

    Article  PubMed  CAS  Google Scholar 

  8. Kim JS, Soucek J, Matousek J, Raines RT. Structural basis for the biological activities of bovine seminal ribonucleases. J Biol Chem 1995; 270:10525.

    Article  PubMed  CAS  Google Scholar 

  9. Cafaro U, De Lorenzo C, Piccoli R, Bracale A, Mastronicola MR, Di Donato A, D’Alessio G. The antitumor action of seminal ribonuclease and its quaternary conformations. FEBS Lett 1995; 359:31.

    Article  PubMed  CAS  Google Scholar 

  10. Kim JS, Soucek J, Matousek J, Raines RT. Mechanism of ribonuclease cytotoxicity. J Biol Chem 1995; 270:31097.

    Article  PubMed  CAS  Google Scholar 

  11. Murthy BS, De Lorenzo C, Piccoli R, D’Alessio G, Sirdeshmukh R. Effects of protein Rnase inhibitor and substrate on the quaternary structures of bovine seminal RNAse. Biochemistry 1996; 35:3880.

    Article  PubMed  CAS  Google Scholar 

  12. Matousek J. The effect of bovine seminal ribonuclease (AS RNase) on cells of Crocker tumour in mice. Experientia 1973; 29:858.

    Article  PubMed  CAS  Google Scholar 

  13. D’Alessio G, Di Donato A, Parente A, Piccoli R. Seminal RNase: a unique member of the ribonuclease superfamily. Trends Biochem Sci 1991; 16:104.

    Article  PubMed  CAS  Google Scholar 

  14. Laccetti P, Spalletti-Cernia D, Portella G, De Corato P, D’Alessio G, Vecchio G. Seminal ribonuclease inhibits tumor growth and reduces the metastatic potential of Lewis lung carcinoma. Cancer Res 1994; 54:4253.

    PubMed  CAS  Google Scholar 

  15. Soucek J, Pouckova P, Matousek J, Stockbauer P, Dostal J, Zadinova M. Antitumor action of bovine seminal ribonuclease. Neoplasma 1996; 43:335.

    PubMed  CAS  Google Scholar 

  16. Pouckova P, Soucek J, Jelinek J, Zadinova M, Hlouskova D, Polivkova J, Navratil L, Cinatl J, Matousek J. Antitumor action of bovine seminal ribonuclease. Cytostatic effect on human melanoma and mouse seminoma. Neoplasma 1998; 45:30.

    PubMed  CAS  Google Scholar 

  17. Pouckova P, Soucek J, Matousek J, Zadinova M, Hlouskova D, Polivkova J, Navratil L. Antitumor action of bovine seminal ribonuclease. Folia Microbiol (Praha) 1998; 43:511.

    Article  CAS  Google Scholar 

  18. Piccoli R, Di Gaetano S, De Lorenzo C, Grauso M, Monaco C, Spalletti-Cernia D, Laccetti P, Cinatl J, Matousek J, D’Alessio G. A dimeric mutant of human pancreatic ribonu-clease with selective cytotoxicity toward malignant cells. Proc Natl Acad Sci U S A 1999; 96:7768.

    Article  PubMed  CAS  Google Scholar 

  19. Kotchetkov R, Cinatl J, Matousek J, Vogel J, Pouckova P, Wagner M, Kornhuber B, Schwabe D, Cinatl J. Bovine seminal ribonuclease inhibits in vivo growth of human neuroblastoma cells. Oncol Rep 2000; 7:363.

    PubMed  CAS  Google Scholar 

  20. Soucek J, Matousek J, Chudomel V, Lindnerova G. Inhibitory effect of bovine seminal ribonuclease on activated lymphocyte and lymphoblastoid cell lines in vitro. Folia Biol (Praha) 1981; 25:334.

    Google Scholar 

  21. Matousek J, Soucek J, Riha J, Zankel TR, Benner SA. Immunosuppressive activity of angiogenin in comparison with bovine seminal ribonuclease and pancreatic ribonuclease. Comp Biochem Physiol Biochem Mol Biol 1995; 112:235.

    Article  CAS  Google Scholar 

  22. Soucek J, Marinov I, Benes J, Hilgert I, Matousek J, Raines RT. Immunosuppressive activity of bovine seminal ribonuclease and its mode of action. Immunobiology 1996; 195:271.

    PubMed  CAS  Google Scholar 

  23. Cinatl J Jr, Cinatl J, Kotchetkov R, Vogel JU, Woodcock BG, Matousek J, Pouckova P, Kornhuber B. Bovine seminal ribonuclease selectively kills human multidrug-resistant neuroblastoma cells via induction of apoptosis. Int J Oncol 1999; 15:1001.

    PubMed  CAS  Google Scholar 

  24. Soucek J, Chudonel V, Potmesilova I, Novak JT. Effect of ribonucleases on cell-mediated lympholysis reaction and on GM-CFC colonies in bone marrow culture. Nat Immun Cell Growth Regul 1986; 5:250.

    PubMed  CAS  Google Scholar 

  25. Loveland BE, Johns TG, MacKay IR, Vaillant F, Wang ZX, Hertzog J. Validation of the MTT dye assay for enumeration of cells in proliferative and antiproliferative assays. Biochem Int 1992; 27:501.

    PubMed  CAS  Google Scholar 

  26. Darzynkiewick Z, Bruno S, Del Bino G, Gorczyca W, Holz MA, Lassota P, Traganos F. Features of apoptotic cells measured by flow cytometry. Cytometry 1992; 13:795.

    Article  Google Scholar 

  27. Mastronicola MR, Piccoli R, D’Alessio G. Key extracellular and intracellular steps in the antitumor action of seminal ribonuclease. Eur J Biochem 1995; 230:242.

    Article  PubMed  CAS  Google Scholar 

  28. Leland PA, Schultz W, Kim BM, Raines RT. Ribonuclease A variants with potent cytotoxic activity. Proc Natl Acad Sci U S A 1998; 95:10407.

    Article  PubMed  CAS  Google Scholar 

  29. Suzuki M, Saxena SK, Boix E, Prill RJ, Vasandani VM, Ladner JE, Sung C, Youle RJ. Engineering receptor-mediated cytotoxicity into human ribonucleases by steric blockade of inhibitor interaction. Nat Biotechnol 1999; 17:265.

    Article  PubMed  CAS  Google Scholar 

  30. Filipec M, Haskova Z, Havrlikova K, Letko E, Holan V, Matousek J, Kalousek I. Immunosuppressive effect of bovine seminal ribonuclease on a model of corneal transplantation in rabbit. Graefes Arch Clin Exp Ophthalmol 1996; 234:586.

    Article  PubMed  CAS  Google Scholar 

  31. Gilloteaux J, Jamison JM, Arnold D, Ervin E, Eckroat L, Docherty JJ, Neal D, Summers JL. Cancer cell necrosis by autoschizis: synergism of antitumor activity of vitamin C: vitamin K3 on human bladder carcinoma T24 cells. Scanning 1998; 20:564.

    PubMed  CAS  Google Scholar 

  32. Vescia S, Tramontano D, Augusti-Tocco G, D’Alessio G. In vitro studies on selective inhibition of tumor cell growth by seminal ribonuclease. Cancer Res 1980; 40:3740.

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dipartimento di Scienze Biomediche, Sezione di Biologia Generale, Cellulare e Genetica Molecolare, Università degli Studi di Catania, Via Androne 81, 95124, Catania, Italy

    F. Sinatra & M. Patania

  2. Dipartimento di Scienze Biomediche, Sezione di Patologia Clinica ed Oncologia Molecolare, Università degli Studi di Catania, Via Androne 87, 95124, Catania, Italy

    D. Callari, M. T. Longombardo, L. Litrico, G. Emmanuele, E. Lanteri & S. Travali

  3. Istituto di Chimica Biologica, Università degli Studi di Catania, Viale A. Doria 6, 95125, Catania, Italy

    M. Viola

  4. Dipartimento di Scienze Farmacologiche, Università degli Studi di Palermo, Via del Vespro 129, 90127, Palermo, Italy

    N. D’Alessandro

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  1. F. Sinatra
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  2. D. Callari
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  3. M. Viola
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Sinatra, F., Callari, D., Viola, M. et al. Bovine seminal RNase induces apoptosis in normal proliferating lymphocytes. Int J Clin Lab Res 30, 191–196 (2000). https://doi.org/10.1007/s005990070006

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  • DOI: https://doi.org/10.1007/s005990070006

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