Prostaglandin-induced programmed cell death in Trypanosoma brucei involves oxidative stress.
Recently, we reported the induction of a programmed cell death (PCD) in bloodstream forms of Trypanosoma brucei by prostaglandin D(2) (PGD(2)). As this prostanoid is readily metabolized in the presence of albumin, we were prompted to investigate if PGD(2) metabolites rather than PGD(2) itself are responsible for the observed PCD. In fact, J series metabolites, especially PGJ(2) and Delta(12)PGJ(2), were able to induce PCD more efficiently than PGD(2). However, the stable PGD(2) analog 17phenyl-trinor-PGD(2) led to the same phenotype as the natural PGD(2), indicating that the latter induces PCD as well. Interestingly, the intracellular reactive oxygen species (ROS) level increased significantly under J series metabolites treatment and, incubation with N-acetyl-L-cysteine or glutathione reduced ROS production and cell death significantly. We conclude that PGJ(2) and Delta(12)PGJ(2) formation within the serum represents a mechanism to amplify PGD(2)-induced PCD in trypanosomes via ROS production.
Figarella
K
K
Interfaculty Institute of Biochemistry, University of Tuebingen, Germany.
Uzcategui
N L
NL
Beck
A
A
Schoenfeld
C
C
Kubata
B K
BK
Lang
F
F
Duszenko
M
M
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D016054:DNA, Protozoan / Q000378:metabolism; D008564:Membrane Potentials; D008854:Microscopy, Electron; D008928:Mitochondria / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D010718:Phosphatidylserines / Q000378:metabolism; D015230:Prostaglandin D2 / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D014346:Trypanosoma brucei brucei / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism
D016054:DNA, Protozoan; D010718:Phosphatidylserines; D017382:Reactive Oxygen Species; C499810:delta(12)-prostaglandin J(2); C037112:9-deoxy-delta-9-prostaglandin D2; D015230:Prostaglandin D2