%0 Journal Article
%T Staurosporine-Induced Cell Death in <em>Trypanosoma brucei</em> and the Role of Endonuclease G during Apoptosis
%A Torsten Barth
%A Gustavo Bruges
%A Andreas Meiwes
%A Stefan Mogk
%A Celestin N. Mudogo
%A Michael Duszenko
%J Open Journal of Apoptosis
%P 16-31
%@ 2168-3840
%D 2014
%I Scientific Research Publishing
%R 10.4236/ojapo.2014.32003
%X Apoptosis in single-cell organisms like <em>Trypanosoma </em>or<em> Leishmania </em>was characterized in several studies in the last few years [1]-[4]. Cell death in these caspase lacking protozoa is still poorly understood and a conclusive apoptotic pathway has not been identified so far. In the work presented here, we studied the effects of prostaglandin D<sub>2</sub> and staurosporine induced cell death in blood-forms of <em>Trypanosoma brucei </em>in a time dependent manner and focused on the role of a nuclease similar to endonuclease G of higher eukaryotes. We found that these parasites undergo apoptotic cell death as demonstrated by the appearance of several canonical hallmarks of apoptosis in higher eukaryotes, but that different stimuli induce remarkable differences in the way these cells die. We compared the effects of prostaglandin D<sub>2</sub> and staurosporine in trypanosomes with and without endonuclease G overexpression by flow cytometric and electron microscopic methods with the result that endonuclease G overexpression led to a significant modification of intracellular organelles and accelerated apoptotic cell death in prostaglandin D<sub>2</sub> or staurosporine treated cells. Our results demonstrate that different stimuli induce apoptosis even in these ancient organisms in different caspase-independent ways. Whereas central processes of apoptosis like ROS formation, loss of mitochondrial membrane potential, endonuclease G release, phosphatidylserine exposure and DNA fragmentation appeared in the same chronology during treatment with either one of both drugs, other effects like cell cycle arrest or change of cell shape occurred only in the case of prostaglandin D<sub>2</sub> or staurosporine treatment. We conclude from these results that trypanosomes react to stimuli of apoptosis with the concerted action of cellular responses but cannot control the final outcome if additional stress, as in the case of staurosporine, is superimposed.
%K &lt
%K em&gt
%K Trypanosoma brucei&lt
%K /em&gt
%K Endonuclease
%K EndoG
%K Staurosporine
%K Programmed Cell Death
%K Apoptosis
%U http://www.scirp.org/journal/PaperInformation.aspx?PaperID=45074