Relationship of chloroquine-induced redistribution of a neutral aminopeptidase to hemoglobin accumulation in malaria parasites.
To study the relationship between neutral aminopeptidase activity and hemoglobin accumulation in malaria parasites, we treated mice infected with Plasmodium berghei NYU-2 with chloroquine intraperitoneally in doses ranging from 0.3 to 3 micromol per 25 g mouse. Preparations of infected erythrocytes (normalized to represent 1000 parasites per 1000 erythrocytes) hydrolyzed 1200 nmol of leucine-p-nitroanilide per minute per milliliter of packed erythrocytes, which was 10x more than that of uninfected preparations. The activity in infected preparations was distinguished by resistance to ferriprotoporphyrin IX and puromycin and susceptibility to inhibition by ethanol and Tris. Chloroquine treatment caused the activity in unwashed membrane ghosts of infected preparations to decrease by 50% despite an increase in total activity. Concomitantly, hemoglobin in washed membrane ghosts increased. Electron microscopy revealed that the hemoglobin was retained in endocytic vesicles. Chloroquine-induced redistribution of a neutral aminopeptidase may be the cause of hemoglobin accumulation in endocytic vesicles of malaria parasites.
Fitch
Coy D
CD
Department of Internal Medicine, Saint Louis University School of Medicine, 1402 South Grand Boulevard, Saint Louis, MO 63104, USA. fitchcd@slu.edu
Cai
Guang-zuan
GZ
Chen
Yi-feng
YF
Ryerse
Jan S
JS
D000626:Aminopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism* / Q000494:pharmacology; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D002738:Chloroquine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004705:Endocytosis; D004910:Erythrocyte Membrane / Q000469:parasitology; D004912:Erythrocytes / Q000378:metabolism / Q000469:parasitology; D006427:Hemin / Q000494:pharmacology; D006454:Hemoglobins / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008288:Malaria / Q000469:parasitology*; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D010962:Plasmodium berghei / Q000378:metabolism*; D011691:Puromycin / Q000494:pharmacology; D013696:Temperature; D013997:Time Factors; D014344:Trypanocidal Agents / Q000494:pharmacology
D000813:Anilides; D000962:Antimalarials; D006454:Hemoglobins; D014344:Trypanocidal Agents; D011691:Puromycin; C001536:1-leucine-4-nitroanilide; D006427:Hemin; D002738:Chloroquine; D000626:Aminopeptidases; C472412:neutral aminopeptidase, Plasmodium berghei