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Using Fluorescent Proteins to Monitor Glycosome Dynamics in the African Trypanosome
Published on: August 19, 2014
Prostaglandin-induced programmed cell death in Trypanosoma brucei involves oxidative stress
K Figarella1, N L Uzcategui, A Beck
1Interfaculty Institute of Biochemistry, University of Tuebingen, Germany.
Cell Death and Differentiation
|February 4, 2006
Summary
Prostaglandin J2 (PGJ2) and Delta(12)PGJ2 metabolites, not PGD2 itself, induce programmed cell death in Trypanosoma brucei. These metabolites increase reactive oxygen species (ROS), leading to trypanosome death.
Area of Science:
- Biochemistry
- Parasitology
- Cell Biology
Background:
- Prostaglandin D2 (PGD2) was previously shown to induce programmed cell death (PCD) in Trypanosoma brucei.
- PGD2 is metabolized in serum, prompting investigation into the role of its metabolites in PCD induction.
Purpose of the Study:
- To determine if PGD2 metabolites, rather than PGD2 itself, are responsible for PCD in Trypanosoma brucei.
- To elucidate the mechanism of PGD2-induced PCD, focusing on reactive oxygen species (ROS) production.
Main Methods:
- Treatment of Trypanosoma brucei with PGD2, its stable analog (17phenyl-trinor-PGD2), and J series metabolites (PGJ2, Delta(12)PGJ2).
- Measurement of intracellular reactive oxygen species (ROS) levels.
- Assessment of cell death induction and mitigation using antioxidants like N-acetyl-L-cysteine and glutathione.
Main Results:
- J series metabolites, PGJ2 and Delta(12)PGJ2, were more potent inducers of PCD than PGD2.
- A stable PGD2 analog induced the same PCD phenotype, confirming PGD2's role.
- Treatment with J series metabolites significantly increased intracellular ROS levels.
- Antioxidant treatment with N-acetyl-L-cysteine or glutathione reduced ROS production and cell death.
Conclusions:
- PGJ2 and Delta(12)PGJ2 are the primary inducers of PCD in Trypanosoma brucei, acting via ROS production.
- Serum metabolism of PGD2 to PGJ2 and Delta(12)PGJ2 amplifies PGD2-induced PCD in trypanosomes.
- ROS generation is a key mechanism in PGD2 metabolite-induced trypanosome cell death.
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