Role of a differentially expressed cAMP phosphodiesterase in regulating the induction of resistance against oxidative damage in Leishmania donovani

Bhattacharya, Arijit ; Biswas, Arunima ; 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. ISSN 0891-5849

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Official URL: http://linkinghub.elsevier.com/retrieve/pii/S08915...

Related URL: http://dx.doi.org/10.1016/j.freeradbiomed.2009.08.025

Abstract

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.

Item Type:Article
Source:Copyright of this article belongs to Society for Free Radical Biology and Medicine.
Keywords:Leishmania Donovani; Macrophage; Oxidative Stress; cAMP Phosphodiesterase; Free Radicals
ID Code:30491
Deposited On:23 Dec 2010 13:28
Last Modified:31 May 2011 05:34

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