ArticleThe Biochemical journal2000
Plasmodium falciparum-infected red blood cells depend on a functional glutathione de novo synthesis attributable to an enhanced loss of glutathione.
Article in The Biochemical journal, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 100 citations in OpenAlex.
- PfPI3K inhibition reversed artemisinin resistance by increasing ROS and ubiquitinated protein levels in Plasmodium falciparum.Communications biology · 2025Article
- Article
- Evaluating phytochemical constituents andHeliyon · 2023Article
- Reactive Oxygen Species as the Brainbox in Malaria Treatment.Antioxidants (Basel, Switzerland) · 2021Review
- Redox interactome in malaria parasite Plasmodium falciparum.Parasitology research · 2021Review
- A disrupted transsulphuration pathway results in accumulation of redox metabolites and induction of gametocytogenesis in malaria.Scientific reports · 2017Article
- Evidence for a role of hemozoin in metabolism and gametocytogenesis.MalariaWorld journal · 2017Article
- Role and Regulation of Glutathione Metabolism in Plasmodium falciparum.Molecules (Basel, Switzerland) · 2015Review
- Buthionine sulfoximine increases the efficacy of arteether antimalarial activity in arteether-resistantMalariaWorld journal · 2015Article
- Glutathione transport: a new role for PfCRT in chloroquine resistance.Antioxidants & redox signaling · 2013Article
- Explaining variance of avian malaria infection in the wild: the importance of host density, habitat, individual life-history and oxidative stress.BMC ecology · 2013Article
- 1,4-naphthoquinones and other NADPH-dependent glutathione reductase-catalyzed redox cyclers as antimalarial agents.Current pharmaceutical design · 2013Review
- Real-time imaging of the intracellular glutathione redox potential in the malaria parasite Plasmodium falciparum.PLoS pathogens · 2013Article
- Degrees of chloroquine resistance in Plasmodium - is the redox system involved?International journal for parasitology. Drugs and drug resistance · 2012Article
- Implication of glutathione in the in vitro antiplasmodial mechanism of action of ellagic acid.PloS one · 2012Article
- Dissecting the role of glutathione biosynthesis in Plasmodium falciparum.Molecular microbiology · 2012Article
- Genetic analysis in mice identifies cysteamine as a novel partner for artemisinin in the treatment of malaria.Mammalian genome : official journal of the International Mammalian Genome Society · 2011Review
- Plasmodium falciparum glutamate dehydrogenase a is dispensable and not a drug target during erythrocytic development.Malaria journal · 2011Article
- Antimalarial and antioxidant activities of methanolic extract of Nigella sativa seeds (black cumin) in mice infected with Plasmodium yoelli nigeriensis.Parasitology research · 2011Article
- Molecular genetics evidence for the in vivo roles of the two major NADPH-dependent disulfide reductases in the malaria parasite.The Journal of biological chemistry · 2010Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During the erythrocytic cycle, Plasmodium falciparum is highly dependent on an adequate thiol status for its survival. Glutathione reductase as well as de novo synthesis of GSH are responsible for the maintenance of the intracellular GSH level. The first and rate-limiting step of the synthetic pathway is catalysed by gamma-glutamylcysteine synthetase (gamma-GCS). Using L-buthionine-(S, R)-sulphoximine (BSO), a specific inhibitor of the gamma-GCS, we show that the infection with P. falciparum causes drastic changes in the GSH metabolism of red blood cells (RBCs). Infected RBCs lose GSH at a rate 40-fold higher than non-infected RBCs. The de novo synthesis of the tripeptide was found to be essential for parasite survival. GSH depletion by BSO inhibits the development of P. falciparum with an IC(50) of 73 microM. The effect of the drug is abolished by supplementation with GSH or GSH monoethyl ester. Our studies demonstrate that the plasmodicidal effect of the inhibitor BSO does not depend on its specificity towards its target enzyme in the parasite, but on the changed physiological needs for the metabolite GSH in the P. falciparum-infected RBCs. Therefore the depletion of GSH is proposed as a chemotherapeutic strategy for malaria, and gamma-GCS is proposed as a potential drug target.
Indexed as
Identifiers
10677377PMC1220884W2147975415What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.