Inhibition of hemoglobin degradation in Plasmodium falciparum by chloroquine and ammonium chloride.
The effect of chloroquine (CQ) and NH4Cl on hemoglobin degradation within Plasmodium falciparum was studied by SDS gel electrophoresis. CQ inhibited hemoglobin digestion such that accumulation of hemoglobin in the parasites occurred. Quantitative analysis indicated that the content of hemoglobin in isolated CQ-treated parasites was increased from 2.39 +/- 0.47 micrograms hemoglobin (Hb)/mg protein to 8.34 +/- 0.77 micrograms Hb/mg protein (P less than 0.001) within 45 min and further to 18.7 +/- 1.23 micrograms Hb/mg protein for 2 hr compared with the untreated parasites. These results suggest that the inhibition of hemoglobin degradation in malarial parasites might be the primary target of CQ antimalarial action. The CQ-like effect on the hemoglobin digestion in P. falciparum was observed with another lysosomotropic weak base, NH4Cl, suggesting that the CQ effect on hemoglobin degradation and its antimalarial action, as well as the effect of NH4Cl, are related to their properties of lysosomotropic weak base.
Zhang
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Institut für Biochemie II, Heidelberg, Federal Republic of Germany.
D000643:Ammonium Chloride / Q000494:pharmacology*; D000818:Animals; D002738:Chloroquine / Q000494:pharmacology*; D004063:Digestion; D004591:Electrophoresis, Polyacrylamide Gel; D006427:Hemin / Q000378:metabolism; D006454:Hemoglobins / Q000378:metabolism*; D010963:Plasmodium falciparum / Q000187:drug effects*
D006454:Hemoglobins; D000643:Ammonium Chloride; D006427:Hemin; D002738:Chloroquine