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Role of intracellular cAMP in differentiation-coupled induction of resistance against oxidative damage in Leishmania donovani

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Title Role of intracellular cAMP in differentiation-coupled induction of resistance against oxidative damage in Leishmania donovani
 
Creator Bhattacharya, Arijit
Biswas, Arunima
Das, Pijush K
 
Subject Infectious Diseases and Immunology
 
Description Even though the human parasite Leishmania donovani encounters tremendous oxidative burst during macrophage invasion, a set of parasites
survives and proliferates intracellularly, leading to transformation from promastigote to amastigote form and disease manifestation. The striking shifts in
temperature (from 22°C in the insect gut to 37°C in the mammalian host) and pH (7.2 in the insect gut to 5.5 in the parasitophorous vacuole of
macrophages) are the key environmental triggers for differentiation as these cause an arrest in the G1 stage of the cell cycle and initiate transformation.
Using an established in vitro culture and differentiation system our study demonstrates that the differentiation-triggering environment induces resistance
to oxidative damage and consequently enhances infectivity. Differentiation conditions caused a three- to fourfold elevation in cAMP level as well as
cAMP-dependent protein kinase activity. Similar to stress exposure, positive modulation of intracellular cAMP resulted in blockage of cell cycle
progression and induction of resistance against oxidative damage. Resistance against pro-oxidants from either stress or cAMP may be associated with
upregulation of the expression of three major antioxidant genes, peroxidoxin 1, trypanothione reductase, and superoxide dismutase A. Positive
modulation of the intracellular cAMP response enables cells to resist the cytotoxic effects of pro-oxidants. In contrast, downregulation of intracellular
cAMP by overexpression of cAMP phosphodiesterase A resulted in a decrease in resistance against oxidative damage and reduced infectivity toward
activated macrophages. This study for the first time reveals the importance of cAMP response in the life cycle and infectivity of the Leishmania parasite.
 
Publisher Elsevier
 
Date 2008
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/1325/1/amader_paper.pdf
Bhattacharya, Arijit and Biswas, Arunima and Das, Pijush K (2008) Role of intracellular cAMP in differentiation-coupled induction of resistance against oxidative damage in Leishmania donovani. Free Radical Biology & Medicine, 44 (5). pp. 779-794.
 
Relation http://dx.doi.org/10.1016/j.freeradbiomed.2007.10.059
http://www.eprints.iicb.res.in/1325/