Prostaglandin-induced programmed cell death in Trypanosoma brucei involves oxidative stress

Abstract

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 D 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 D 12 PGJ 2 formation within the serum represents a mechanism to amplify PGD 2 -induced PCD in trypanosomes via ROS production.

15-Deoxy-Δ(12,14)-prostaglandin J2 Induces Vascular Endothelial Cell Apoptosis through the Sequential Activation of MAPKS and p53

“…NAC, a precursor molecule for glutathione (GSH) synthesis, is usually used to monitor the effect of GSH supplementation in vitro. In particular, GSH is an important antioxidant that protects cells from oxidative damage by ROS, although it has been found that 15d-PGJ 2 induces cell death by decrease of the intracellular level of GSH (43)(44)(45). Therefore, it is possible that the GSH depletion may be an early molecular event, leading to triggering of 15d-PGJ 2 -induced oxidative stress responses in HUVECs and in vascular ECs of cornea.…”

Disturbance of redox status enhances radiosensitivity of hepatocellular carcinoma

“…The cells were pelleted by centrifugation and washed twice with PBS to remove the background fluorescence. Stained cells were analyzed using a flow cytometer (Becton Dickinson, Heidelberg, Germany) in combination with Flow Jo software [29].…”

Staurosporine-Induced Cell Death in <em>Trypanosoma brucei</em> and the Role of Endonuclease G during Apoptosis

“…While it is thus a significant contributor to the functional development and maintenance of multicellular organisms, the advantages of apoptosis for unicellular organisms are much less evident. Nevertheless, apoptosis or apoptosis-like phenotypes have been described in many different single-cell eukaryotes, such as yeast [7] [8], Tetrahymena [9], Dictyostelium [10], and different kinetoplastids like trypanosomes [3] and leishmania [1] [4]. It has also been suggested that apoptosis may even occur in bacteria [11] [12].…”

“…It has also been suggested that apoptosis may even occur in bacteria [11] [12]. In T. brucei, apoptosis contributes to cell density regulation [3] and acts as a mechanism to maintain genetic stability and differentiation [13].…”

“…PGD 2 is a prostanoid derived from arachidonic acid via the cyclooxygenase pathway. In T. brucei, PGD 2 is produced and secreted by the stumpy bloodform and induces an apoptosis-like cell death which includes intra-cellular ROS formation, phosphatidylserine exposure, loss of mitochondrial membrane potential and DNA degradation [3]. The stumpy bloodform was also shown to be more sensitive to PGD 2 than the slender bloodform, suggesting that the physiological function of PGD 2 is related to the parasite's cell density regulation and acts therefore in favour of a balanced parasite-host interrelationship [2] [22].…”