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Leishmania donovani: Dyskinetoplastid cells survive and proliferate in the presence of pyruvate and uridine but do not undergo apoptosis after treatment with camptothecin

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Title Leishmania donovani: Dyskinetoplastid cells survive and proliferate in the presence of pyruvate and uridine but do not undergo apoptosis after treatment with camptothecin
 
Creator Sen, N
Banerjee, B
Sen Gupta, S
Das, BB
Ganguly, A
Majumder, HK
 
Subject Parasitology
 
Description We have shown that treatment with luteolin in leishmanial cells causes loss of mt-DNA and induces apoptosis through mitochondria dependent pathway [Sen, N., Das, B.B., Ganguly, A., Banerjee, B., Sen, T., Majumder, H.K., 2006. Leishmania donovani: intracellular ATP level regulates apoptosis-like death in luteolin induced dyskinetoplastid cells. Experimental Parasitology, in press]. Here, we report that mitochondrial DNA depleted leishmanial cells require exogenous sources of pyruvate and uridine to survive and proliferate. The presence of pyruvate and uridine in a growing media help them to produce sufficient amount of glycolytic ATP to maintain the mitochondrial membrane potential in the absence of their functional ETC. Treatment of wild type cells with CPT causes generation of ROS that leads to apoptosis. But unlike the normal cells ROS was not generated in these mt-DNA depleted cells after treatment with CPT. Taken together we have shown for the first time that dyskinetoplastid cells are auxotrophic for pyruvate and uridine and apoptosis cannot be induced in these cells in the presence of CPT. Therefore, the presence of mitochondrial DNA is absolutely necessary for the cytotoxicity of CPT in kinetoplastid parasites. (c) 2006 Elsevier Inc. All rights reserved.
 
Publisher ACADEMIC PRESS INC ELSEVIER SCIENCESAN DIEGO525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA
 
Date 2011-09-20T12:12:41Z
2011-09-20T12:12:41Z
2007
 
Type Article
 
Identifier EXPERIMENTAL PARASITOLOGY
0014-4894
http://hdl.handle.net/123456789/14383
 
Language English