MODULATION OF PROTEIN-KINASE-C ACTIVITY IN PLASMODIUM-FALCIPARUM - INFECTED ERYTHROCYTES

Infection of human erythrocytes with the malaria parasite Plasmodium f alciparum induces many morphological and biochemical changes in the ho st cell. Host serine/threonine protein kinases could be involved in so me of these processes. The aim of this study was to determine the effe ct of infection on red blood cell protein kinase C (PKC) and establish the importance of this enzyme in parasite growth and sexual stage dif ferentiation. Phorbol myristate acetate (PMA)-induced translocation of erythrocyte PKC activity is impaired in erythrocytes enriched for mat ure 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 f rom whole cell lysates by DE52 chromatography suggests that total acti vatable PKC levels are lower in infected erythrocytes, A reduction in PMA-induced activation is also observed in PKC assays performed in sit u. Downregulation of erythrocyte PKC by overnight incubation with PMA before infection causes a significant decrease in the rate of the asex ual growth, suggesting that the enzyme, although lost later in infecti on, may be important in the earlier development of the parasite. By co ntrast, the lack of PKC had no effect on the production of sexual stag e parasites. (C) 1997 by The American Society of Hematology.