Plasmodium falciparum: effects of proteinase inhibitors on globin hydrolysis by cultured malaria parasites.
The effects of peptide proteinase inhibitors on globin hydrolysis by cultured malaria parasites were studied. All of the four cysteine proteinase inhibitors evaluated blocked globin hydrolysis, as documented by the development of a morphological abnormality in which parasite food vacuoles filled with undegraded globin and by SDS-PAGE showing that the cysteine proteinase inhibitor-treated parasites accumulated large quantities of globin. The aspartic proteinase inhibitor pepstatin did not block globin hydrolysis by cultured parasites. None of seven antimalarial drugs tested elicited the food vacuole abnormality caused by cysteine proteinase inhibitors, indicating that this morphological alteration was not simply a sign of nonspecific parasite toxicity. Our results indicate that a trophozoite cysteine proteinase is required for initial cleavages of globin by intact malaria parasites.
Rosenthal
P J
PJ
Department of Medicine, San Francisco General Hospital, California.
D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D002918:Chymotrypsin / Q000037:antagonists & inhibitors; D003374:Coumarins / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D004151:Dipeptides / Q000378:metabolism / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology*; D005456:Fluorescent Dyes / Q000378:metabolism; D005914:Globins / Q000378:metabolism*; D006801:Humans; D006868:Hydrolysis / Q000187:drug effects; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D007976:Leupeptins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D010436:Pepstatins / Q000494:pharmacology; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D014617:Vacuoles / Q000187:drug effects / Q000378:metabolism
D000962:Antimalarials; D003374:Coumarins; D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D005456:Fluorescent Dyes; D007976:Leupeptins; D009842:Oligopeptides; D010436:Pepstatins; C092609:benzyloxycarbonyl-phenylalanyl-arginine fluoromethane; C014195:Streptomyces pepsin inhibitor; C021159:benzyloxycarbonyl-phenylalanylarginine-4-methylcoumaryl-7-amide; D005914:Globins; C002101:chymostatin; D002918:Chymotrypsin; D007930:Leucine; C032854:leupeptin; C024974:E 64; C031375:pepstatin