The Caspase-independent Algorithm of Programmed Cell Death in Leishmania Induced by Baicalein: the Role of LdEndoG, LdFEN-1 and LdTatD as a DNA ‘degradesome’
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
The Caspase-independent Algorithm of Programmed
Cell Death in Leishmania Induced by Baicalein: the Role
of LdEndoG, LdFEN-1 and LdTatD as a DNA
‘degradesome’
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| Creator |
Bose Dasgupta, Somdeb
Das, BB Sengupta, S Ganguly, A Roy, A Dey, S Tripath, G Dinda, B Majumder, Hemanta K |
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| Subject |
Chemistry
Infectious Diseases and Immunology |
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| Description |
In the post-genomic perspective, the quest of programmed cell death (PCD) mechanisms in kinetoplastid parasites lies in the
identification and characterization of cell death executer proteins. Here, we show that baicalein (BLN), a potent topoisomerase IB
inhibitor, generates an oxidative stress in the parasites leading to altered physiological and morphological parameters, which
are characteristic of PCD. For the first time we elucidate that, caspase-independent activation of a novel effector molecule,
endonuclease G (LdEndoG), mediates BLN-induced cell death. Functional characterization of LdEndoG identifies Flap
endonuclease-1 (LdFEN-1) and LdTatD-like nuclease as other effector molecules. BLN treatment translocates LdEndoG from
mitochondria to nucleus, where it forms separate complexes with LdFEN-1 and LdTatD to constitute a DNA ‘degradesome’
unique to these parasites. Conditional antisense knockdown of LdEndoG provides protection against PCD. This knowledge
paves the path toward a better understanding of the PCD pathway in simpler systems, which could be exploited in antileishmanial
chemotherapy.
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| Date |
2008
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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/147/1/CELL_DEATH_AND_DIFFERENTIATION%2C15(10)%2C1629%2D1640%2C2008[31].pdf
Bose Dasgupta, Somdeb and Das, BB and Sengupta, S and Ganguly, A and Roy, A and Dey, S and Tripath, G and Dinda, B and Majumder, Hemanta K (2008) The Caspase-independent Algorithm of Programmed Cell Death in Leishmania Induced by Baicalein: the Role of LdEndoG, LdFEN-1 and LdTatD as a DNA ‘degradesome’. Cell Death and Differentiation, 15 (10). pp. 1629-1640. |
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| Relation |
http://dx.doi.org/10.1038/cdd.2008.85
http://www.eprints.iicb.res.in/147/ |
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