Please use this identifier to cite or link to this item:
|Title:||Drug-induced permeabilization of parasite's digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum||Authors:||Ch'ng, J.-H.
Lysosomal membrane permeabilization
Programmed cell death
|Issue Date:||Oct-2011||Citation:||Ch'ng, J.-H., Liew, K., Goh, A.S.-P., Sidhartha, E., Tan, K.S.-W. (2011-10). Drug-induced permeabilization of parasite's digestive vacuole is a key trigger of programmed cell death in Plasmodium falciparum. Cell Death and Disease 2 (10) : -. ScholarBank@NUS Repository. https://doi.org/10.1038/cddis.2011.97||Abstract:||Having previously characterized chloroquine (CQ)-induced programmed cell death (PCD) hallmarks in the malaria parasite Plasmodium falciparum and delineating a pathway linking these features, the roles of non-classical mediators were investigated in this paper. It was shown that the later stages of this pathway are Ca2 +-dependent and transcriptionally regulated. Moreover, it was demonstrated for the first time that micromolar concentrations of CQ partially permeabilized the parasite's digestive vacuole (DV) membrane and that this important upstream event appears to precede mitochondrial dysfunction. This permeabilization of the DV occurred without rupture of the DV membrane and was reminiscent of lysosome-mediated cell death in mammalian cells. As such micromolar concentrations of CQ are found in the patient's plasma after initial CQ loading, this alludes to a clinically relevant antimalarial mechanism of the drug which has yet to be recognized. Furthermore, other 'non-antimalarial' lysosomotropic compounds were also shown to cause DV permeabilization, triggering PCD in both CQ-sensitive and -resistant parasites. These findings present new avenues for antimalarial developments, which induce DV destabilization to kill parasites. © 2011 Macmillan Publishers Limited.||Source Title:||Cell Death and Disease||URI:||http://scholarbank.nus.edu.sg/handle/10635/126720||ISSN:||20414889||DOI:||10.1038/cddis.2011.97|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Sep 29, 2022
WEB OF SCIENCETM
checked on Sep 29, 2022
checked on Sep 22, 2022
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.