Camptothecin-induced Imbalance in Intracellular Cation Homeostasis Regulates Programmed Cell Death in Unicellular Hemoflagellate Leishmania donovani
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Camptothecin-induced Imbalance in Intracellular Cation
Homeostasis Regulates Programmed Cell Death in Unicellular
Hemoflagellate Leishmania donovani
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| Creator |
Sen, Nilkantha
Das, Benu Brata Ganguly, Agneyo Mukherjee, Tanmoy Bandyopadhyay, Santu Majumder, Hemanta K |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Leishmania, a unicellular trypanosomatid protozoan
parasite, causes a wide range of human diseases ranging
from the localized self-healing cutaneous lesions to fatal
visceral leishmaniasis. However, it undergoes a process
of programmed cell death during treatment with the
topoisomerase I poison camptothecin (CPT). The present
study shows that CPT-induced formation of reactive
oxygen species increases the level of cytosolic calcium
through the release of calcium ions from intracellular
stores as well as by influx of extracellular calcium. Elevation
of cytosolic calcium is responsible for depolarization
of mitochondrial membrane potential (��m), which
is followed by a significant decrease in intracellular pH
levels. CPT-induced oxidative stress also causes impairment
of the Na�-K�-ATPase pump and subsequently decreases
the intracellular K� level in leishmanial cells. A
decrease in both intracellular pH and K� levels propagates
the apoptotic process through activation of
caspase 3-like proteases by rapid formation of cytochrome
c-mediated apoptotic complex. In addition to
caspase-like protease activation, a lower level of intracellular
K� also enhances the activation of apoptotic
nucleases at the late stage of apoptosis. This suggests
that the physiological level of pH and K� are inhibitory
for apoptotic DNA fragmentation and caspase-like protease
activation in leishmanial cells. Moreover, unlike
mammalian cells, the intracellular ATP level gradually
decreases with an increase in the number of apoptotic
cells after the loss of ��m. Taken together, the elucidation
of biochemical events, which tightly regulate the
process of growth arrest and death of Leishmania donovani
promastigotes, allows us to define a more comprehensive
view of cell death during treatment with CPT.
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| Publisher |
American Society for Biochemistry and Molecular Biology
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| Date |
2004
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| Type |
Article
PeerReviewed |
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| Format |
application/pdf
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| Identifier |
http://www.eprints.iicb.res.in/530/1/JOURNAL_OF_BIOLOGICAL_CHEMISTRY%2C__279(_50)%2C__52366%2D52375__[2].pdf
Sen, Nilkantha and Das, Benu Brata and Ganguly, Agneyo and Mukherjee, Tanmoy and Bandyopadhyay, Santu and Majumder, Hemanta K (2004) Camptothecin-induced Imbalance in Intracellular Cation Homeostasis Regulates Programmed Cell Death in Unicellular Hemoflagellate Leishmania donovani. The Journal of Biological Chemistry, 279 (50). pp. 52366-52375. |
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| Relation |
http://dx.doi.org/10.1074/jbc.M406705200
http://www.eprints.iicb.res.in/530/ |
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