The online version of this article (doi:10.1186/1475-2875-11-297) contains supplementary material, which is available to authorized users.
The authors declare that they have no competing interests
HM, MA, JH and HS performed the experiments and statistical analysis. VC and AU assisted with experiments. HH conceived the study and drafted the manuscript. HM, MA, JH and HS assisted with the study design and drafting of the manuscript and all authors read and approved the final manuscript.
Plasmodium berghei ookinetes exhibit an apoptotic phenotype when developing within the mosquito midgut lumen or when cultured in vitro. Markers of apoptosis increase when they are exposed to nitric oxide or reactive oxygen species but high concentrations of hydrogen peroxide cause death without observable signs of apoptosis. Chloroquine and other drugs have been used to induce apoptosis in erythrocytic stages of Plasmodium falciparum and to formulate a putative pathway involving cysteine protease activation and mitochondrial membrane permeabilization; initiated, at least in the case of chloroquine, after its accumulation in the digestive vacuole causes leakage of the vacuole contents. The lack of a digestive vacuole in ookinetes prompted the investigation of the effect of chloroquine and staurosporine on this stage of the life cycle. Finally, the suggestion that apoptosis may have evolved as a strategy employed by ookinetes to increase the fitness of surviving parasites was explored by determining whether increasing the ecological triggers parasite density and nutrient depletion induced apoptosis.
Ookinetes were grown in culture then either exposed to hydrogen peroxide, chloroquine or staurosporine, or incubated at different densities and in different media. The proportion of ookinetes displaying positive markers for apoptosis in treated samples was compared with controls and results were analyzed using analysis of variance followed by a Turkey’s test, or a Kruskal-Wallis test as appropriate.
Hydrogen peroxide below 50 μM triggered apoptosis but cell membranes were rapidly compromised by higher concentrations, and the mode of death could not be defined. Both chloroquine and staurosporine cause a significant increase in ookinetes with condensed chromatin, caspase-like activity and, in the case of chloroquine, phosphatidylserine translocation and DNA fragmentation (not investigated for staurosporine). However, mitochondrial membrane potential remained intact. No relationship between ookinete density and apoptosis was detected but nutrient depletion significantly increased the proportion of ookinetes with chromatin condensation in four hours.
It is proposed that both a mitochondrial and an amitochondrial apoptotic pathway may be involved, dependent upon the trigger that induces apoptosis, and that pathways may differ between erythrocytic stages and ookinetes, or between rodent and human malaria parasites.
Authors’ original file for figure 112936_2012_2462_MOESM1_ESM.bmp
Authors’ original file for figure 212936_2012_2462_MOESM2_ESM.bmp
Authors’ original file for figure 312936_2012_2462_MOESM3_ESM.bmp
Authors’ original file for figure 412936_2012_2462_MOESM4_ESM.bmp
Authors’ original file for figure 512936_2012_2462_MOESM5_ESM.bmp
Hurd H, Carter V, Nacer A: Interactions between malaria and mosquitoes: the role of apoptosis in parasite establishment and vector response to infection. Curr Top Microbiol Immunol. 2005, 289: 185-217. 10.1007/3-540-27320-4_9. PubMed
Ali M, Al-Olayan EM, Lewis S, Matthews H, Hurd H: Naturally occurring triggers that induce apoptosis-like programmed cell death in Plasmodium berghei ookinetes. PLoS One. 2010, 5: 12634-10.1371/journal.pone.0012634. CrossRef
Nedelcu AM: Comparative genomics of phylogenetically diverse unicellular Eukaryotes provide new insights into the genetic basis for the evolution of the programmed cell death machinery. J MolEvol. 2009, 68: 256-268.
Kaczanowski S, Sajid M, Reece SE: Evolution of apoptosis-like programmed cell death in unicellular protozoan parasites. Parasit Vects. 2011, 4: 44-10.1186/1756-3305-4-44. CrossRef
Rathore S, Jain S, Sinha D, Gupta M, Asad M, Srivastava A, Narayanan MS, Ramasamy G, Chauhan VS, Gupta D, Mohmmed A: Disruption of a mitochondrial protease machinery in Plasmodium falciparum is an intrinsic signal for parasite cell death. Cell Death Dis. 2011, 2: e231-10.1038/cddis.2011.118. PubMedCentralCrossRefPubMed
Suradji EW, Hatabu T, Kobayashi K, Yamazaki C, Abdulah R, Nakazawa M, Nakajima-Shimada J, Koyama H: Selenium-induced apoptosis-like cell death in Plasmodium falciparum. Parasitology. 2011, 138: 1-11. CrossRef
Arambage SC: An in vitro study of apoptosis-like cell death in Plasmodium berghei. 2008, Institute for Science and Technology in Medicine: Keele University
Salvioli S, Ardizzoni A, Franceschi C, Cossarizza A: JC-1, but not DiOC(6)(3) or rhodamine 123, is a reliable fluorescent probe to assess Delta Psi changes in intact cells: Implications for studies on mitochondrial functionality during apoptosis. FEBS Lett. 1997, 411: 77-82. 10.1016/S0014-5793(97)00669-8. CrossRefPubMed
Kroemer G, Galluzzi L, Vandenabeele P, Abrams J, Alnemri ES, Baehrecke EH, Blagosklonny MV, El-Deiry WS, Golstein P, Green DR, Hengartner M, Knight RA, Kumar S, Lipton SA, Malorni W, Nuňez G, Peter ME, Tschopp J, Yuan J, Piacentini M, Zhivotovsky B, Melino G: Classification of cell death: recommendations of the Nomenclature Committee on Cell Death 2009. Cell Death Differ. 2009, 16: 3-11. 10.1038/cdd.2008.150. PubMedCentralCrossRefPubMed
Galluzzi L, Aaronson SA, Abrams J, Alnemri ES, Andrews DW, Baehrecke EH, Bazan NG, Blagosklonny MV, Blomgren K, Borner C, Bredesen DE, Brenner C, Castedo M, Cidlowski JA, Ciechanover A, Cohen GM, De Laurenzi V, De Maria R, Deshmukh M, Dynlacht BD, El-Deiry WS, Flavell RA, Fulda S, Garrido C, Golstein P, Gougeon ML, Green DR, Gronemeyer H, Hajnoczky G, Hardwick JM, Hengartner MO, Ichijo H, Jaattela M, Kepp O, Kimchi A, Klionsky DJ, Knight RA, Kornbluth S, Kumar S, Levine B, Lipton SA, Lugli E, Madeo F, Malorni W, Marine JCW, Martin SJ, Medema JP, Mehlen P, Melino G, Moll UM, Morselli E, Nagata S, Nicholson DW, Nicotera P, Nunez G, Oren M, Penninger J, Pervaiz S, Peter ME, Piacentini M, Prehn JHM, Puthalakath H, Rabinovich GA, Rizzuto R, Rodrigues CMP, Rubinsztein DC, Rudel T, Scorrano L, Simon HU, Steller H, Tschopp J, Tsujimoto Y, Vandenabeele P, Vitale I, Vousden KH, Youle RJ, Yuan J, Zhivotovsky B, Kroemer G: Guidelines for the use and interpretation of assays for monitoring cell death in highereukaryotes. Cell Death Differ. 2009, 16: 1093-1107. 10.1038/cdd.2009.44. PubMedCentralCrossRefPubMed
- Variation in apoptosis mechanisms employed by malaria parasites: the roles of inducers, dose dependence and parasite stages
- BioMed Central
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II