Apoptosis is Induced in leishmanial Cells by a Novel Protein Kinase Inhibitor Withaferin A and is Facilitated by Apoptotic Topoisomerase I–DNA complex
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
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| Title |
Apoptosis is Induced in leishmanial Cells by a Novel
Protein Kinase Inhibitor Withaferin A and is Facilitated
by Apoptotic Topoisomerase I–DNA complex
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| Creator |
Sen, N
Banerjee, B Ganguly, A Sen, T Pramanik, S Mukhopadhyay, S Majumder, Hemanta K |
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| Subject |
Infectious Diseases and Immunology
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| Description |
Protein kinase C (PKC) is an important constituent of the signaling pathways involved in apoptosis. We report here that like staurosporine, withaferin A is a potent inhibitor of PKC. In Leishmania donovani, the inhibition of PKC by withaferin A causes depolarization of DWm and generates ROS inside cells. Loss of DWm leads to the release of cytochrome c into the cytosol and subsequently activates caspase-like proteases and oligonucleosomal DNA cleavage. Moreover, in treated cells, oxidative DNA lesions facilitate the stabilization of topoisomerase I-mediated cleavable complexes, which also contribute to DNA
fragmentation. However, withaferin A and staurosporine cannot induce cleavable complex formation in vitro with recombinant topoisomerase I nor with nuclear extracts from control cells. Taken together, our results indicate that inhibition of PKC by withaferin A is a central event for the induction of apoptosis and that the stabilization of topoisomerase I–DNA complex is necessary to amplify apoptotic process.
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| Date |
2007
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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/367/1/CELL_DEATH_AND_DIFFERENTIATION%2C_14_(_2)%2C_358%2D367%2C2007_[119].pdf
Sen, N and Banerjee, B and Ganguly, A and Sen, T and Pramanik, S and Mukhopadhyay, S and Majumder, Hemanta K (2007) Apoptosis is Induced in leishmanial Cells by a Novel Protein Kinase Inhibitor Withaferin A and is Facilitated by Apoptotic Topoisomerase I–DNA complex. Cell Death and Differentiation , 14 (2). pp. 358-367. |
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| Relation |
http://dx.doi.org/10.1038/sj.cdd.4402002
http://www.eprints.iicb.res.in/367/ |
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