Original ContributionRole of a differentially expressed cAMP phosphodiesterase in regulating the induction of resistance against oxidative damage in Leishmania donovani
Section snippets
Parasite and cell culture
Pathogenic strains of L. donovani, AG83 (MHOM/IN/1983/AG83) and GE1 (MHOM/IN/89/GE1), were maintained in susceptible BALB/c mice and cultured as promastigotes in medium 199 (Invitrogen, Carlsbad, CA, USA) with Hanks’ salt containing Hepes (12 mM), l-glutamine (20 mM), 10% heat-inactivated FCS, 50 U/ml penicillin, and 50 μg/ml streptomycin. The promastigotes were obtained by culturing infected spleens in medium M199 for 5 days at 22°C. The adherent murine macrophage cell line RAW 264.7 was
Intracellular cAMP induces resistance to hydrogen peroxide and peroxynitrite
At the onset of mammalian infection, L. donovani promastigotes encounter a huge shift in temperature from 22°C in the insect gut to 37°C in the mammalian host and a shift of pH from 7.4 in sandfly gut to 5.5 in parasitophorous vacuoles of macrophages. We showed earlier that exposure to such temperature and pH renders the promastigotes more resistant to H2O2 and peroxynitrite (ONOO−) and this was associated with an increase in intracellular cAMP level [13]. Similar to stress exposure, resistance
Discussion
Mining of the Leishmania genome revealed the presence of genes associated with the cAMP signaling pathway, and our previous work showed that differentiation conditions can induce resistance to oxidative damage via a cAMP-mediated response in L. donovani [13]. However, a defined participation of any of those genes in environmental sensing as well as in differentiation-coupled events is yet to be determined. The results of this study show that differentiation-coupled depletion of a cytosolic cAMP
Acknowledgments
This work was funded by the Department of Science and Technology and a Network Project grant (NWP 0038) from the Council of Scientific and Industrial Research (Government of India).
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These authors contributed equally to this work.