title: Modulation of protein kinase C activity in Plasmodium falciparum-infected erythrocytes.
abstract: Infection of human erythrocytes with the malaria parasite Plasmodium falciparum induces many morphological and biochemical changes in the host cell. Host serine/threonine protein kinases could be involved in some of these processes. The aim of this study was to determine the effect of infection on red blood cell protein kinase C (PKC) and establish the importance of this enzyme in parasite growth and sexual stage differentiation. Phorbol myristate acetate (PMA)-induced translocation of erythrocyte PKC activity is impaired in erythrocytes enriched for mature asexual stage infected cells. Western blotting shows that this is due to a relative reduction in membrane PKC protein levels rather than inhibition of enzyme activity and analysis of PKC activity isolated from whole cell lysates by DE52 chromatography suggests that total activatable PKC levels are lower in infected erythrocytes. A reduction in PMA-induced activation is also observed in PKC assays performed in situ. Downregulation of erythrocyte PKC by overnight incubation with PMA before infection causes a significant decrease in the rate of the asexual growth, suggesting that the enzyme, although lost later in infection, may be important in the earlier development of the parasite. By contrast, the lack of PKC had no effect on the production of sexual stage parasites.
authors.affiliation: Department of Medical Parasitology, London School of Hygiene and Tropical Medicine, UK.
authors.forename: B S
authors.initials: BS
authors.lastname: Hall
authors.forename: O O
authors.initials: OO
authors.lastname: Daramola
authors.forename: G
authors.initials: G
authors.lastname: Barden
authors.forename: G A
authors.initials: GA
authors.lastname: Targett
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000032:analysis / Q000378:metabolism*; D004912:Erythrocytes / Q000201:enzymology / Q000469:parasitology*; D006801:Humans; D016778:Malaria, Falciparum / Q000201:enzymology*; D010963:Plasmodium falciparum; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D017868:Cyclic AMP-Dependent Protein Kinases; D013755:Tetradecanoylphorbol Acetate