Activation of protein kinase C by phorbol esters disrupts the tegument of Schistosoma mansoni

Abstract

The tegument of the human parasite Schistosoma mansoni is critical for parasite survival within the mammalian host. The role of protein kinase C (PKC), a major effector molecule in the phosphoinositide pathway, in maintaining the structural organization of this syncytial layer was examined in adult worms. Phorbol 12-myristate, 13-acetate (PMA) and phorbol 12,13-dibutyrate (PDB), phorbol esters that activate PKC, induced formation of surface vesicles as determined by light and scanning electron microscopy. Similar results were seen with sn-2-dioctanoyl-glycerol, a synthetic analogue of diacylglycerol. No effect was seen in parasites incubated with 4-alpha-phorbol ester or alpha isomers of PMA or PDB, compounds that do not activate PKC. Vesicle formation was reversible in parasites treated with sn-2-dioctanoyl-glycerol but not with phorbol esters. The tegument of male worms was more sensitive to the effect of phorbol esters than females. Transmission electron microscopy revealed vacuolization of the tegument. These data suggest that signal transduction pathways may have a critical role in the maintenance of the structural integrity of the tegument of parasitic helminths.

Protein Kinase C and Extracellular Signal-Regulated Kinase Regulate Movement, Attachment, Pairing and Egg Release in Schistosoma mansoni

“…Live adult worms were also exposed to 1 µM PMA for 30 min in an attempt to identify other regions displaying PKC activation. In these specimens, activation was evident in similar regions to those observed without PMA treatment; however, generally more activation was observed at the tegument surface (Figure 6L), and evidence of tegument disruption was apparent in some specimens in response to PMA, as has been reported by other authors [61]. Activated PKC was also found to be associated with the lumen of the vitellaria, more extensive portions of the oesophagus and the muscular ventral sucker (Figures 6M–O).…”

In Vitro and In Vivo Activities of Arachidonic Acid against Schistosoma mansoni and Schistosoma haematobium

“…The tegumental ultrastructure of adult S. mansoni and S. haematobium worms incubated for 4 h in RPMI medium supplemented with 20% FCS and 0 mM ARA appeared intact (33) (Fig. 2A).…”

“…Worms were monitored for motility, contractility, and viability every hour for a 5-h incubation period at 37°C and 5% CO 2 , and 24 h after the worms were washed and incubated in drug-free RPMI medium-20% FCS. ARA-treated juvenile and adult worms were washed in FCS-free RPMI medium and processed for scanning and transmission electron microscopy as described previously (33).…”

Early post-larval development of the endoparasitic platyhelminthMesocestoides corti: Trypsin provokes reversible tegumental damage leading to serum-induced cell proliferation and growth

“…There are some examples of agents that stimulate cestode larval development while reversibly disrupt tegument. That is the case of PKC activators in Schistosoma mansoni (Wiest et al, 1994), praziquantel in M. corti (Britos et al, 2000), and N-lauroyl sarcosinate in Mesocestoides vogae (Hrckova et al, 1998), which concomitantly increased larvae segmentation rates and induced morphological damage on their surfaces. Likewise, bile salts, such as sodium taurocholate, stimulate cestode development (Smyth and Davies, 1974;Esch and Smyth, 1976;Kawamoto et al, 1986;Saldana et al, 2001Saldana et al, , 2003.…”