Role of a Differentially Expressed cAMP Phosphodiesterase in Regulating the Induction of Resistance against Oxidative Damage in Leishmania Donovani
IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata
View Archive Info| Field | Value | |
| Title |
Role of a Differentially Expressed cAMP Phosphodiesterase in Regulating the Induction of Resistance against Oxidative Damage in Leishmania Donovani
|
|
| Creator |
Bhattacharyya, Arijit
Biswas, Arumina Das, Pijush K |
|
| Subject |
Infectious Diseases and Immunology
|
|
| Description |
Differentiation-coupled induction of resistance of Leishmania parasites to macrophage oxidative damage was
shown to be associated with an increased cAMP response. This study explores the significance of the cAMP
response in the parasite by identifying a differentially expressed cAMP phosphodiesterase (LdPDEA) and
deciphering its role in regulating antioxidant machineries in the parasite. LdPDEA, a high KM class I cytosolic
cAMP phosphodiesterase, was expressed maximally in log-phase promastigotes, but was significantly
reduced in stationary-phase promastigotes and amastigotes. Chemical inhibition or silencing of PDEA
conferred enhanced resistance to pro-oxidants in these cells and this led to studies on trypanothione
biosynthesis and utilization, as trypanothione is one of the major modulators of antioxidant defense in
kinetoplastidae. Despite enhanced arginase and ornithine decarboxylase activity, trypanothione biosynthesis
seemed to be unaffected by PDEA blockage, whereas significant elevations in the expression of tryparedoxin
peroxidase, ascorbate peroxidase, and tryparedoxin were detected, suggesting a definite shift of
trypanothione-pool utilization bias toward antioxidant defense. Moreover, parasites that overexpressed
PDEA showed reduced resistance to oxidative damage and reduced infectivity toward activated
macrophages. This study reveals the significance of a cAMP phosphodiesterase in the infectivity of Leishmania
parasites.
|
|
| Date |
2009
|
|
| Type |
Article
PeerReviewed |
|
| Format |
application/pdf
|
|
| Identifier |
http://www.eprints.iicb.res.in/959/1/4_frbm_2009.pdf
Bhattacharyya, Arijit and Biswas, Arumina and Das, Pijush K (2009) Role of a Differentially Expressed cAMP Phosphodiesterase in Regulating the Induction of Resistance against Oxidative Damage in Leishmania Donovani. Free Radical Biology & Medicine, 47 (10). pp. 1494-1506. |
|
| Relation |
http://dx.doi.org/10.1016/j.freeradbiomed.2009.08.025
http://www.eprints.iicb.res.in/959/ |
|