Asexual blood stages of Plasmodium falciparum exhibit signs of secondary necrosis, but not classical apoptosis after exposure to febrile temperature (40 C).
It has been shown by others that after cultures of Plasmodium falciparum were exposed to a febrile temperature of 40 C, parasitemia was reduced in the subsequent generation, suggesting a temperature-induced inhibition of trophozoites and schizonts. In the current study, influences unique to cultivation were ruled out, demonstrating that 40 C impacted the parasites directly. Metabolic profiling of DNA synthesis, protein synthesis, and glucose utilization clearly indicated that febrile temperatures had a direct effect on parasite development, beginning 20-24 hr after erythrocyte invasion. The mechanism of parasite death was investigated for evidence of temperature-induced apoptosis. Lack of typical physiological hallmarks, namely, caspase activation, characteristic mitochondrial membrane potential changes, and DNA degradation as indicated by DNA laddering, eliminated 'classical' apoptosis as a mechanism of parasite death. Parasites dying under the influence of heat, staurosporine, and chloroquine initially appeared pyknotic by light and electron microscopy (as in apoptosis), but eventual swelling and lysis of the food vacuole membrane led to secondary necrosis. Chloroquine did induce DNA laddering, but it was later attributed to occult white blood cell contaminants. While not apoptosis, the results do not rule out other forms of temperature-induced programmed cell death.
Porter
Heidi
H
Department of Microbiology and Molecular Biology, Brigham Young University, Provo, Utah 84602, USA. heidiporter@byu.edu
Gamette
Matthew J
MJ
Cortes-Hernandez
Dania G
DG
Jensen
James B
JB
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D017209:Apoptosis; D020169:Caspases / Q000378:metabolism; D002738:Chloroquine / Q000494:pharmacology; D053938:DNA Fragmentation; D016054:DNA, Protozoan / Q000096:biosynthesis / Q000378:metabolism; D004789:Enzyme Activation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004912:Erythrocytes / Q000469:parasitology*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000502:physiology; D046529:Microscopy, Electron, Transmission; D009336:Necrosis; D010963:Plasmodium falciparum / Q000166:cytology* / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D015800:Protozoan Proteins / Q000096:biosynthesis; D019311:Staurosporine / Q000494:pharmacology; D013696:Temperature
D000962:Antimalarials; D016054:DNA, Protozoan; D004791:Enzyme Inhibitors; D015800:Protozoan Proteins; D002738:Chloroquine; D020169:Caspases; D019311:Staurosporine; D005947:Glucose