Leishmania major: Effect of protein kinase A and phosphodiesterase activity on infectivity and proliferation of promastigotes |
| |
Authors: | Laura Malki-Feldman |
| |
Affiliation: | Kuvin Center for the Study of Infectious and Tropical Diseases, Department of Microbiology and Molecular Genetics, P.O. Box 12272, Hebrew University, Hadassah Medical School, Jerusalem 91120, Israel |
| |
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. |
| |
Keywords: | cAMP dependent protein kinase Protein kinase G Leishmania major Signal transduction Phosphodiesterase 8-CPT-cAMP Sp-cAMPS-AM |
本文献已被 ScienceDirect 等数据库收录! |
|