1887

Abstract

Previous studies have shown that the protozoan parasite exhibits apoptotic features with caspase-like activity upon exposure to a cytotoxic monoclonal antibody or the anti-parasitic drug metronidazole. The present study reports that staurosporine (STS), a common apoptosis inducer in mammalian cells, also induces cytoplasmic and nuclear features of apoptosis in , including cell shrinkage, phosphatidylserine (PS) externalization, maintenance of plasma membrane integrity, extensive cytoplasmic vacuolation, nuclear condensation and DNA fragmentation. STS-induced PS exposure and DNA fragmentation were abolished by the mitochondrial transition pore blocker cyclosporine A and significantly inhibited by the broad-range cysteine protease inhibitor iodoacetamide. Interestingly, the apoptosis phenotype was insensitive to inhibitors of caspases and cathepsins B and L, while calpain-specific inhibitors augmented the STS-induced apoptosis response. While the identities of the proteases responsible for STS-induced apoptosis warrant further investigation, these findings demonstrate that programmed cell death in is complex and regulated by multiple mediators.

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2010-05-01
2020-04-09
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References

  1. Al-Olayan E. M., Williams G. T., Hurd H.. 2002; Apoptosis in the malaria protozoan, Plasmodium berghei: a possible mechanism for limiting intensity of infection in the mosquito. Int J Parasitol32:1133–1143
    [Google Scholar]
  2. Alvarez V. E., Kosec G., Sant Anna C., Turk V., Cazzulo J. J., Turk B.. 2008; Blocking autophagy to prevent parasite differentiation: a possible new strategy for fighting parasitic infections?. Autophagy4:361–363
    [Google Scholar]
  3. Ameisen J. C., Idziorek T., Billaut-Mulot O., Loyens M., Tissier J. P., Potentier A., Ouaissi A.. 1995; Apoptosis in a unicellular eukaryote ( Trypanosoma cruzi): implications for the evolutionary origin and role of programmed cell death in the control of cell proliferation, differentiation and survival. Cell Death Differ2:285–300
    [Google Scholar]
  4. Andiran N., Acikgoz Z. C., Turkay S., Andiran F.. 2006; Blastocystis hominis – an emerging and imitating cause of acute abdomen in children. J Pediatr Surg41:1489–1491
    [Google Scholar]
  5. Arnoult D., Tatischeff I., Estaquier J., Girard M., Sureau F., Tissier J. P., Grodet A., Dellinger M., Traincard F.. other authors 2001; On the evolutionary conservation of the cell death pathway: mitochondrial release of an apoptosis-inducing factor during Dictyostelium discoideum cell death. Mol Biol Cell12:3016–3030
    [Google Scholar]
  6. Arnoult D., Akarid K., Grodet A., Petit P. X., Estaquier J., Ameisen J. C.. 2002; On the evolution of programmed cell death: apoptosis of the unicellular eukaryote Leishmania major involves cysteine proteinase activation and mitochondrion permeabilization. Cell Death Differ9:65–81
    [Google Scholar]
  7. Baehrecke E. H.. 2002; How death shapes life during development. Nat Rev Mol Cell Biol3:779–787
    [Google Scholar]
  8. Bera A., Singh S., Nagaraj R., Vaidya T.. 2003; Induction of autophagic cell death in Leishmania donovani by antimicrobial peptides. Mol Biochem Parasitol127:23–35
    [Google Scholar]
  9. Blomgren K., Zhu C. L., Wang X. Y., Karlsson J. O., Leverin A. L., Bahr B. A., Mallard C., Hagberg H.. 2001; Synergistic activation of caspase-3 by m-calpain after neonatal hypoxia-ischemia – a mechanism of “pathological apoptosis”?. J Biol Chem276:10191–10198
    [Google Scholar]
  10. Bortner C. D., Cidlowski J. A.. 1998; A necessary role for cell shrinkage in apoptosis. Biochem Pharmacol56:1549–1559
    [Google Scholar]
  11. Broker L. E., Kruyt F. A. E., Giaccone G.. 2005; Cell death independent of caspases: a review. Clin Cancer Res11:3155–3162
    [Google Scholar]
  12. Chose O., Noel C., Gerbod D., Brenner C., Viscogliosi E., Roseto A.. 2002; A form of cell death with some features resembling apoptosis in the amitochondrial unicellular organism Trichomonas vaginalis. Exp Cell Res276:32–39
    [Google Scholar]
  13. Christensen S. T., Chemnitz J., Straarup E. M., Kristiansen K., Wheatley D. N., Rasmussen L.. 1998; Staurosporine-induced cell death in Tetrahymena thermophila has mixed characteristics of both apoptotic and autophagic degeneration. Cell Biol Int22:591–598
    [Google Scholar]
  14. Cirioni O., Giacometti A., Drenaggi D., Ancarani F., Scalise G.. 1999; Prevalence and clinical relevance of Blastocystis hominis in diverse patient cohorts. Eur J Epidemiol15:389–393
    [Google Scholar]
  15. Collins J. A., Schandi C. A., Young K. K., Vesely J., Willingham M. C.. 1997; Major DNA fragmentation is a late event in apoptosis. J Histochem Cytochem45:923–934
    [Google Scholar]
  16. Cornillon S., Foa C., Davoust J., Buonavista N., Gross J. D., Golstein P.. 1994; Programmed cell death in Dictyostelium. J Cell Sci107:2691–2704
    [Google Scholar]
  17. Croft S. L., Sundar S., Fairlamb A. H.. 2006; Drug resistance in leishmaniasis. Clin Microbiol Rev19:111–126
    [Google Scholar]
  18. Deponte M.. 2008; Programmed cell death in protists. Biochim Biophys Acta 1783;1396–1405
    [Google Scholar]
  19. Deponte M., Becker K.. 2004; Plasmodium falciparum – do killers commit suicide?. Trends Parasitol20:165–169
    [Google Scholar]
  20. Fidock D. A., Eastman R. T., Ward S. A., Meshnick S. R.. 2008; Recent highlights in antimalarial drug resistance and chemotherapy research. Trends Parasitol24:537–544
    [Google Scholar]
  21. Gao G., Dou Q. P.. 2000; N-terminal cleavage of Bax by calpain generates a potent proapoptotic 18-kDa fragment that promotes Bcl-2-independent cytochrome c release and apoptotic cell death. J Cell Biochem80:53–72
    [Google Scholar]
  22. Hengartner M. O.. 2000; The biochemistry of apoptosis. Nature407:770–776
    [Google Scholar]
  23. Ho L. C., Singh M., Suresh G., Ng G. C., Yap E. H.. 1993; Axenic culture of Blastocystis hominis in Iscove's modified Dulbecco's medium. Parasitol Res79:614–616
    [Google Scholar]
  24. Kobayashi T., Endoh H.. 2005; A possible role of mitochondria in the apoptotic-like programmed nuclear death of Tetrahymena thermophila. FEBS J272:5378–5387
    [Google Scholar]
  25. Kroemer G., Galluzzi L., Brenner C.. 2007; Mitochondrial membrane permeabilization in cell death. Physiol Rev87:99–163
    [Google Scholar]
  26. Kubbutat M. H., Vousden K. H.. 1997; Proteolytic cleavage of human p53 by calpain: a potential regulator of protein stability. Mol Cell Biol17:460–468
    [Google Scholar]
  27. Lantsman Y., Tan K. S., Morada M., Yarlett N.. 2008; Biochemical characterization of a mitochondrial-like organelle from Blastocystis sp. subtype 7. Microbiology154:2757–2766
    [Google Scholar]
  28. Madeo F., Herker E., Maldener C., Wissing S., Lächelt S., Herlan M., Fehr M., Lauber K., Sigrist S. J.. other authors 2002; A caspase-related protease regulates apoptosis in yeast. Mol Cell9:911–917
    [Google Scholar]
  29. Mariante R. M., Vancini R. G., Benchimol M.. 2006; Cell death in trichomonads: new insights. Histochem Cell Biol125:545–556
    [Google Scholar]
  30. McDonald M. C., Mota-Filipe H., Paul A., Cuzzocrea S., Abdelrahman M., Harwood S., Plevin R., Chatterjee P. K., Yaqoob M. M., Thiemermann C.. 2001; Calpain inhibitor I reduces the activation of nuclear factor- κB and organ injury/dysfunction in hemorrhagic shock. FASEB J15:171–186
    [Google Scholar]
  31. Nasirudeen A. M., Tan K. S.. 2004; Caspase-3-like protease influences but is not essential for DNA fragmentation in Blastocystis undergoing apoptosis. Eur J Cell Biol83:477–482
    [Google Scholar]
  32. Nasirudeen A. M., Tan K. S.. 2005; Programmed cell death in Blastocystis hominis occurs independently of caspase and mitochondrial pathways. Biochimie87:489–497
    [Google Scholar]
  33. Nasirudeen A. M., Singh M., Yap E. H., Tan K. S.. 2001a; Blastocystis hominis: evidence for caspase-3-like activity in cells undergoing programmed cell death. Parasitol Res87:559–565
    [Google Scholar]
  34. Nasirudeen A. M. A., Tan K. S. W., Singh M., Yap E. H.. 2001b; Programmed cell death in a human intestinal parasite, Blastocystis hominis. Parasitology123:235–246
    [Google Scholar]
  35. Nasirudeen A. M., Hian Y. E., Singh M., Tan K. S.. 2004; Metronidazole induces programmed cell death in the protozoan parasite Blastocystis hominis. Microbiology150:33–43
    [Google Scholar]
  36. Stechmann A., Hamblin K., Perez-Brocal V., Gaston D., Richmond G. S., van der Giezen M., Clark C. G., Roger A. J.. 2008; Organelles in Blastocystis that blur the distinction between mitochondria and hydrogenosomes. Curr Biol18:580–585
    [Google Scholar]
  37. Stensvold C. R., Nielsen H. V., Molbak K., Smith H. V.. 2009; Pursuing the clinical significance of Blastocystis – diagnostic limitations. Trends Parasitol25:23–29
    [Google Scholar]
  38. Tafani M., Minchenko D. A., Serroni A., Farber J. L.. 2001; Induction of the mitochondrial permeability transition mediates the killing of HeLa cells by staurosporine. Cancer Res61:2459–2466
    [Google Scholar]
  39. Tan K. S.. 2004; Blastocystis in humans and animals: new insights using modern methodologies. Vet Parasitol126:121–144
    [Google Scholar]
  40. Tan K. S.. 2008; New insights on classification, identification, and clinical relevance of Blastocystis spp. Clin Microbiol Rev21:639–665
    [Google Scholar]
  41. Tan K. S., Nasirudeen A. M.. 2005; Protozoan programmed cell death – insights from Blastocystis deathstyles. Trends Parasitol21:547–550
    [Google Scholar]
  42. Tan Y., Wu C., De Veyra T., Greer P. A.. 2006; Ubiquitous calpains promote both apoptosis and survival signals in response to different cell death stimuli. J Biol Chem281:17689–17698
    [Google Scholar]
  43. Tasova Y., Sahin B., Koltas S., Paydas S.. 2000; Clinical significance and frequency of Blastocystis hominis in Turkish patients with hematological malignancy. Acta Med Okayama54:133–136
    [Google Scholar]
  44. Taylor R. C., Cullen S. P., Martin S. J.. 2008; Apoptosis: controlled demolition at the cellular level. Nat Rev Mol Cell Biol9:231–241
    [Google Scholar]
  45. Turk B., Stoka V.. 2007; Protease signalling in cell death: caspases versus cysteine cathepsins. FEBS Lett581:2761–2767
    [Google Scholar]
  46. Vardi A., Berman-Frank I., Rozenberg T., Hadas O., Kaplan A., Levine A.. 1999; Programmed cell death of the dinoflagellate Peridinium gatunense is mediated by CO2 limitation and oxidative stress. Curr Biol9:1061–1064
    [Google Scholar]
  47. Vaux D. L., Haecker G., Strasser A.. 1994; An evolutionary perspective on apoptosis. Cell76:777–779
    [Google Scholar]
  48. Weil M., Jacobson M. D., Coles H. S., Davies T. J., Gardner R. L., Raff K. D., Raff M. C.. 1996; Constitutive expression of the machinery for programmed cell death. J Cell Biol133:1053–1059
    [Google Scholar]
  49. Welburn S. C., Dale C., Ellis D., Beecroft R., Pearson T. W.. 1996; Apoptosis in procyclic Trypanosoma brucei rhodesiense in vitro. Cell Death Differ3:229–236
    [Google Scholar]
  50. Zangger H., Mottram J. C., Fasel N.. 2002; Cell death in Leishmania induced by stress and differentiation: programmed cell death or necrosis?. Cell Death Differ9:1126–1139
    [Google Scholar]
  51. Zhang X. D., Gillespie S. K., Hersey P.. 2004; Staurosporine induces apoptosis of melanoma by both caspase-dependent and -independent apoptotic pathways. Mol Cancer Ther3:187–197
    [Google Scholar]
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