This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fitch, C. D. Articles by Chou, A. C. Search for Related Content PubMed PubMed Citation Articles by Fitch, C. D. Articles by Chou, A. C.

 Previous Article  |  Next Article 

Antimicrob. Agents Chemother., 11 1997, 2461-2465, Vol 41, No. 11
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Regulation of heme polymerizing activity and the antimalarial action of chloroquine

CD Fitch and AC Chou
Department of Internal Medicine, Saint Louis University School of Medicine, Missouri 63104, USA. fitchcd@wpogate.slu.edu

Mice infected with Plasmodium berghei served as donors of erythrocytes with a high level of parasitemia for the study of ferriprotoporphyrin IX (FP) polymerization. Six hours after treatment of these mice with 3 micromol of chloroquine per 25 g of body weight, there were significant losses of heme polymerase I (HPA I). For chloroquine-susceptible (CS) P. berghei, the rate of FP polymerization decreased from 541 +/- 42 (mean +/- standard deviation; n = 12) to 51 +/- 19 (n = 8) nmol of FP polymerized per h per ml of packed erythrocytes (normalized to represent 1,000 parasites per 1,000 erythrocytes). For chloroquine- resistant (CR) P. berghei, the rate decreased from 284 +/- 19 (n = 16) to 124 +/- 11 (n = 6) nmol per h per ml. The chloroquine-induced loss of HPA I was accompanied by the accumulation of unpolymerized FP in CS P. berghei but not in CR P. berghei, which is consistent with the hypothesis that FP mediates the antimalarial action of chloroquine. Quinine treatment partially reversed the effects of chloroquine in CS P. berghei but not in CR P. berghei. Cycloheximide treatment antagonized the effects of chloroquine in both lines of parasites. To explain these findings, we propose that chloroquine, quinine, and cycloheximide perturb a regulatory process for HPA I. Furthermore, we propose that when chloroquine engages its target in the regulatory process, it initiates a chain of events which culminates in increased production, accessibility, or reactivity of a regulator (inactivator) of HPA I.

This article has been cited by other articles:

• Fitch, C. D., Chen, Y.-f., Cai, G.-z. (2003). Chloroquine-induced Masking of a Lipid That Promotes Ferriprotoporphyrin IX Dimerization in Malaria. J. Biol. Chem. 278: 22596-22599 [Abstract] [Full Text]  
• Dzierszinski, F., Coppin, A., Mortuaire, M., Dewailly, E., Slomianny, C., Ameisen, J.-C., DeBels, F., Tomavo, S. (2002). Ligands of the Peripheral Benzodiazepine Receptor Are Potent Inhibitors of Plasmodium falciparum and Toxoplasma gondii In Vitro. Antimicrob. Agents Chemother. 46: 3197-3207 [Abstract] [Full Text]