Variation in apoptosis mechanisms employed by malaria parasites: the roles of inducers, dose dependence and parasite stages

Malaria Journal

Research

Victoria Carter¹  Jennifer Hunt¹  Hannah Szor¹  Ann Underhill¹  Hilary Hurd¹  Medhat Ali²  Holly Matthews³ 

[1] Centre for Applied Entomology and Parasitology, Institute for Science and Technology in Medicine, School of Life Sciences, Keele University, Keele, ST5 5BG, Staffordshire, UK;Centre for Applied Entomology and Parasitology, Institute for Science and Technology in Medicine, School of Life Sciences, Keele University, Keele, ST5 5BG, Staffordshire, UK;Department of Zoology, Faculty of Science, Ain Shams University, P.BOX 11566, Cairo, Egypt;Centre for Applied Entomology and Parasitology, Institute for Science and Technology in Medicine, School of Life Sciences, Keele University, Keele, ST5 5BG, Staffordshire, UK;School of Environment and Life Sciences, College of Science and Technology, University of Salford, M5 4WT, Salford, Greater Manchester, UK;

关键词: Apoptosis;    Malaria;    Plasmodium berghei;    Ookinetes;    Chloroquine;    Reactive oxygen species;    Density;   

DOI  :  10.1186/1475-2875-11-297

 received in 2012-06-07, accepted in 2012-08-24,  发布年份 2012

来源: Springer

【 摘 要 】

BackgroundPlasmodium 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.MethodsOokinetes 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.ResultsHydrogen 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.ConclusionsIt 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.

【 授权许可】

Unknown   
© Matthews et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.