Activation of protein kinase C by phorbol esters disrupts the tegument of Schistosoma mansoni.
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.
Wiest
P M
PM
Department of Medicine, Miriam Hospital, Providence, RI.
Kunz
S S
SS
Miller
K R
KR
D000818:Animals; D001700:Biomphalaria / Q000469:parasitology; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008855:Microscopy, Electron, Scanning; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000201:enzymology / Q000648:ultrastructure; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate