Downstream effects of haemoglobinase inhibition in Plasmodium falciparum-infected erythrocytes

• Published in: Molecular and biochemical parasitology Vol. 173; no. 2; pp. 81 - 87
• Main Authors: Naughton, Julie A., Nasizadeh, Sima, Bell, Angus
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.10.2010; Amsterdam: Elsevier
• Subjects: 50% inhibitory concentration; Aminopeptidases; Aminopeptidases - antagonists & inhibitors; Aminopeptidases - metabolism; antagonists & inhibitors; Antimalarial drug; Antimalarials; Antimalarials - pharmacology; Aspartic Acid Endopeptidases; Aspartic Acid Endopeptidases - antagonists & inhibitors; Aspartic Acid Endopeptidases - metabolism; Cysteine Endopeptidases; Cysteine Endopeptidases - metabolism; dimethylsulphoxide; DMSO; drug effects; E-64; Enzyme Inhibitors; Enzyme Inhibitors - pharmacology; enzymology; Erythrocytes; Erythrocytes - parasitology; growth & development; Haemoglobin; hemoglobin; Hemoglobins; Hemoglobins - metabolism; Hemolysis; Humans; IC50; infected red blood cell (erythrocyte); iRBC; l-trans-epoxy-succinyl-leucylamido-(4-guanidino)-butane; MACS; magnet-activated cell sorting; Malaria; metabolism; N-CBZ-phenylalanyl-alanyl-flouromethyl ketone; p.i; parasitology; PBS; Peptidase; pharmacology; phosphate-buffered saline; plasmepsin inhibitor I; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - enzymology; Plasmodium falciparum - growth & development; Plasmodium falciparum - metabolism; PM-I; post-invasion; Protein Biosynthesis; Protein Biosynthesis - drug effects; Protein synthesis; Protozoan Proteins; Protozoan Proteins - antagonists & inhibitors; Protozoan Proteins - metabolism; salt sodium citrate; SSC; Z-FA-FMK; PBS; SSC; Peptidase; Malaria; DMSO; E-64; MACS; Haemoglobin; p.i; Plasmodium falciparum; Protein synthesis; IC50; Antimalarial drug; iRBC; Z-FA-FMK; PM-I

Our data suggest that the likely downstream effect of inhibition of haemoglobin degradation in erythrocytic Plasmodium falciparum is blockade of protein synthesis rather than premature host cell lysis. Blood-stage malarial parasites (Plasmodium falciparum) digest large quantities of host haemoglobin...