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Titolo:
The fate of ferriprotorphyrin IX in malaria infected erythrocytes in conjunction with the mode of action of antimalarial drugs
Autore:
Zhang, JM; Krugliak, M; Ginsburg, H;
Indirizzi:
Hebrewsrael Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904 Jerusalem, I Hebrew Univ Jerusalem Jerusalem Israel IL-91904 m, IL-91904 Jerusalem, I
Titolo Testata:
MOLECULAR AND BIOCHEMICAL PARASITOLOGY
fascicolo: 1, volume: 99, anno: 1999,
pagine: 129 - 141
SICI:
0166-6851(19990315)99:1<129:TFOFII>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PARASITE PLASMODIUM-FALCIPARUM; QUINOLINE-CONTAINING ANTIMALARIALS; RED-BLOOD-CELLS; FERRIPROTOPORPHYRIN-IX; HEME POLYMERASE; BETA-HEMATIN; PHOSPHOLIPID MONOLAYERS; HEMOGLOBIN DEGRADATION; CHLOROQUINE; RESISTANCE;
Keywords:
Plasmodium falciparum; hemoglobin; ferriprotoporphyrin IX; hemozoin; 4-aminoquinolines;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
55
Recensione:
Indirizzi per estratti:
Indirizzo: Ginsburg, H Hebrewsrael Jerusalem, Inst Life Sci, Dept Biol Chem, IL-91904Jerusalem, I Hebrew Univ Jerusalem Jerusalem Israel IL-91904 Jerusalem, I
Citazione:
J.M. Zhang et al., "The fate of ferriprotorphyrin IX in malaria infected erythrocytes in conjunction with the mode of action of antimalarial drugs", MOL BIOCH P, 99(1), 1999, pp. 129-141

Abstract

The intraerythrocytic malaria parasite digests considerable amounts of itshost cell cytosol, which consists mostly of hemoglobin. In order to avert the toxicity of ferriprotorphyrin IX (FP) thus produced, it is generally accepted that FP is polymerized to the non-toxic hemozoin. Investigating the fate of FP in cultured Plasmodium falciparum -infected human red blood cells, revealed a straight correlation between amounts of digested hemoglobin and hemozoin, but the latter contained less FP than produced. The efficacy of FP polymerization is stage-dependent, increasing with parasite maturation. Different strains display dissimilar efficacy in hemozoin production. Unpolymerized FP possibly exits the food vacuole and is degraded by glutathione, thus accounting for the low levels of free FP found in infected cells. 4-aminoquinoline antimalarials demonstrably form complexes with FP and inhibit hemozoin production in vitro. Chloroquine, amodiaquine, quinine and mefloquine were found to inhibit hemozoin production in intact infected cells, but only the first two drugs caused a dose-dependent accumulation of FP in the membrane fraction of infected cells that correlated well with parasite killing, dye to the permeabilization of membranes to ions. This differential effect is explained by the ability of chloroquine and amodiaquine to inhibit the degradation of membrane-associated FP by glutathione and the incapacity of quinine and mefloquine to do so. This discrepancy implies that the antimalarial mode of action of chloroquine and amodiaquine is different in its mechanistic details from that of quinine and mefloquine and is compatible with the diametric sensitivity of most strains to chloroquine and mefloquine and the disparate interaction of these drugs with enhancers of their antimalarial action. (C) 1999 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 27/11/20 alle ore 07:21:22