Leishmania major: Effect of protein kinase A and phosphodiesterase activity on infectivity and proliferation of promastigotes

Laura Malki-Feldman, Charles L. Jaffe*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

Abstract

Effect of modulators on protein kinase A (PKA) activity, promastigote growth and their ability to infect peritoneal macrophages was monitored. PKA inhibitors reduced [Protein Kinase Inhibitor (PKI) - 56%; H89 - 54.5%] kemptide phosphorylation by Leishmania major promastigote lysates, while activators increased phosphorylation (8-CPT-cAMP - 88%; Sp-cAMPS-AM - 152%). Activation was specifically inhibited by PKI. Phosphodiesterase inhibitors also increased kemptide phosphorylation (dipyridamole - 171%; rolipram - 106%; and 3-isobutyl-1-methyl-xanthine - 154%). Parasite proliferation was significantly retarded (200 nM H89; 100 μM myristoylated-PKI) or completely inhibited (500 nM H89) by culturing with PKA inhibitors. Incubation with dipyridamole or Sp-cAMPS-AM also inhibited proliferation. Brief treatment (2 h) with either H89, myristoylated-PKI, dipyridamole or Sp-cAMPS-AM reduced initial macrophage infection at days 1 and 2 (>40%) and on day 3 (>78% only for 100 μM myr-PKI). Characterization of leishmanial cAMP mediated signal transduction pathways will serve as the basis for the new drug design.

Original languageEnglish
Pages (from-to)39-44
Number of pages6
JournalExperimental Parasitology
Volume123
Issue number1
DOIs
StatePublished - Sep 2009

Keywords

  • 8-CPT-cAMP
  • cAMP dependent protein kinase
  • Leishmania major
  • Phosphodiesterase
  • Protein kinase G
  • Signal transduction
  • Sp-cAMPS-AM

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