A parasitophorous duct in Plasmodium-infected red blood cells

Sherman, I.W.; Zidovetzki, Raphael

doi:10.1016/0169-4758(92)90294-c

Cited by 10 publications

(4 citation statements)

References 11 publications

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“…Compounds can enter the food vacuole in the following ways: (i) weak bases, such as chloroquine, accumulating in their protonated form due to the weak base effect; (ii) small hydrophobic molecules passively diffusing across the three membrane systems between the serum and the food vacuole; and (iii) molecules that gain access to the red blood cell cytoplasm being passively transported from the cytoplasm into the food vacuole during hemoglobin ingestion. In addition, there is controversial evidence for a putative parasitophorous duct which directly connects the parasite cytoplasm to the external medium (32,33).…”

Section: Discussionmentioning

confidence: 99%

Inhibition of Hemozoin Formation in Plasmodium falciparum Trophozoite Extracts by Heme Analogs: Possible Implication in the Resistance to Malaria Conferred by the β-Thalassemia Trait

Martiney

Cerami

Slater

1996

Mol Med

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Section: Discussionmentioning

confidence: 99%

Inhibition of Hemozoin Formation in Plasmodium falciparum Trophozoite Extracts by Heme Analogs: Possible Implication in the Resistance to Malaria Conferred by the β-Thalassemia Trait

Martiney

Cerami

Slater

1996

Mol Med

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“…A recent study proposed a novel pathway ofaccess ofsubstances into the parasite via an aqueous duct leading to parasite outer membrane ( 18). The validity of that pathway has been questioned (25) but firmly defended (26). Clearly exogenous agents can gain access to the parasitized cell as a whole by alternative or parallel routes that might lead to different intracellular compartments or even to the same compartments by a combination of parallel and serial routes.…”

Section: Discussionmentioning

confidence: 99%

The antimalarial action of desferal involves a direct access route to erythrocytic (Plasmodium falciparum) parasites.

Loyevsky

Lytton²,

Mester³

et al. 1993

J. Clin. Invest.

102

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We designed the N-methylanthranilic-desferrioxamine (MA-DFO) as a fluorescent iron(III) chelator with improved membrane permeation properties. Upon binding of iron(III), MA-DFO fluorescence is quenched, thus allowing traceability of drug-iron(III) interactions. MA-DFO is well tolerated by mammalian cells in culture. Its antimalarial activity is pronounced: IC50 values on in vitro (24-h) growth of Plasmodium fakciparum were 3±1 MM for MA-DFO compared with 30±8 for DFO. The onset of growth inhibition of rings or trophozoites occurs 2-4 h after exposure to 13 gM MA-DFO. This effect is commensurate with MA-DFO permeation into infected cells. In a 24-h exposure to MA-DFO or DFO, trophozoites take up either compound to -10% of the external concentration, rings to 5%, and noninfected cells to < 1%. Red cells encapsulated with millimolar concentrations of DFO or MA-DFO fully support parasite invasion and growth. We conclude that extracellular MA-DFO and DFO gain selective access into parasites by bypassing the host. The rate-limiting step is permeation through the parasite membrane, which MA-DVO accomplishes faster than DFO, in accordance with its iigher hydrophobicity. These views are consistent with the proposed duct, which apparently provides parasitized cells with a window to the external medium. (J. Clin. Invest. 1993. 91:218-224.)

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“…More recently, larger fluorescent molecules such as Lucifer yellow (141,199) and various fluorescent macromolecule conjugates (138,153,253) have been used in conjunction with fluorescence microscopy to study the uptake of such solutes into individual parasitized erythrocytes. The data are qualitative and, as discussed in section IVC, may, in some cases, be compromised by the dissociation of the fluorophore from the molecules of interest (153,291).…”

Section: Fluorescent Transport Solutesmentioning

confidence: 99%

“…Several others have emphasized potential problems arising from the dissociation of low-molecular-weight fluorophores from the fluorescently labeled probes used in the original study (143,153,291). In particular, Hibbs et al (153), using a combination of confocal and electron microscopy, demonstrated that although incubation of malaria-infected erythrocytes with the fluorescent beads used in the original study by Taraschi and colleagues resulted in fluorescent labeling of the parasite and, in some cases, of associated tubular structures, the beads themselves (which had diameters down to 14 nm, well below that of the putative duct) remained excluded from the parasitized erythrocyte.…”

Section: Does the Parasitized Erythrocyte Take Up Macromolecules And Other High-molecular-weight Solutes?mentioning

confidence: 99%

Membrane Transport in the Malaria-Infected Erythrocyte

Kirk

2001

Physiological Reviews

352

312

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The malaria parasite is a unicellular eukaryotic organism which, during the course of its complex life cycle, invades the red blood cells of its vertebrate host. As it grows and multiplies within its host blood cell, the parasite modifies the membrane permeability and cytosolic composition of the host cell. The intracellular parasite is enclosed within a so-called parasitophorous vacuolar membrane, tubular extensions of which radiate out into the host cell compartment. Like all eukaryote cells, the parasite has at its surface a plasma membrane, as well as having a variety of internal membrane-bound organelles that perform a range of functions. This review focuses on the transport properties of the different membranes of the malaria-infected erythrocyte, as well as on the role played by the various membrane transport systems in the uptake of solutes from the extracellular medium, the disposal of metabolic wastes, and the origin and maintenance of electrochemical ion gradients. Such systems are of considerable interest from the point of view of antimalarial chemotherapy, both as drug targets in their own right and as routes for targeting cytotoxic agents into the intracellular parasite.

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A parasitophorous duct in Plasmodium-infected red blood cells

Cited by 10 publications

References 11 publications

Inhibition of Hemozoin Formation in Plasmodium falciparum Trophozoite Extracts by Heme Analogs: Possible Implication in the Resistance to Malaria Conferred by the β-Thalassemia Trait

Inhibition of Hemozoin Formation in Plasmodium falciparum Trophozoite Extracts by Heme Analogs: Possible Implication in the Resistance to Malaria Conferred by the β-Thalassemia Trait

The antimalarial action of desferal involves a direct access route to erythrocytic (Plasmodium falciparum) parasites.

Membrane Transport in the Malaria-Infected Erythrocyte

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