TY - JOUR
T1 - Leishmania donovani
T2 - Dyskinetoplastid cells survive and proliferate in the presence of pyruvate and uridine but do not undergo apoptosis after treatment with camptothecin
AU - Sen, Nilkantha
AU - Banerjee, Bijoylaxmi
AU - Gupta, Souvik Sen
AU - Das, Benu Brata
AU - Ganguly, Agneyo
AU - Majumder, Hemanta K.
N1 - Funding Information:
We thank Prof. S. Roy, the Director of our institute, for his interest in this work. N.S. is supported by Senior Research Fellowship from the Council for Scientific and Industrial Research; Government of India.
PY - 2007/2
Y1 - 2007/2
N2 - 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.
AB - 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.
KW - 5-(and -6)-chloromethyl-2′
KW - 7′-dichlorodihydro-fluorescein diacetate acetyl ester
KW - Apoptosis-like death
KW - CPT
KW - Camptothecin
KW - Dyskinetoplastidy
KW - ETC
KW - HDCFDA
KW - Leishmania
KW - Luteolin
KW - PCD
KW - ROS
KW - camptothecin
KW - electron transport chain
KW - mitochondrial transmembrane potential
KW - programmed cell death
KW - reactive oxygen species
KW - ΔΨ
UR - http://www.scopus.com/inward/record.url?scp=33751404556&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33751404556&partnerID=8YFLogxK
U2 - 10.1016/j.exppara.2006.08.005
DO - 10.1016/j.exppara.2006.08.005
M3 - Article
C2 - 17027973
AN - SCOPUS:33751404556
SN - 0014-4894
VL - 115
SP - 215
EP - 219
JO - Experimental Parasitology
JF - Experimental Parasitology
IS - 2
ER -