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

Nilkantha Sen, Bijoylaxmi Banerjee, Souvik Sen Gupta, Benu Brata Das, Agneyo Ganguly, Hemanta K. Majumder

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)215-219
Number of pages5
JournalExperimental Parasitology
Volume115
Issue number2
DOIs
StatePublished - Feb 1 2007

Keywords

  • 5-(and -6)-chloromethyl-2′
  • 7′-dichlorodihydro-fluorescein diacetate acetyl ester
  • Apoptosis-like death
  • CPT
  • Camptothecin
  • Dyskinetoplastidy
  • ETC
  • HDCFDA
  • Leishmania
  • Luteolin
  • PCD
  • ROS
  • camptothecin
  • electron transport chain
  • mitochondrial transmembrane potential
  • programmed cell death
  • reactive oxygen species
  • ΔΨ

ASJC Scopus subject areas

  • Parasitology
  • Immunology
  • Infectious Diseases

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