ArticleThe Journal of biological chemistry2010
Glutathione reductase-null malaria parasites have normal blood stage growth but arrest during development in the mosquito.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers, 1 of them a synthesis that pooled it.
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Who cites it
28 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Efficacy and safety of methylene blue in the treatment of malaria: a systematic review.BMC medicine · 2018Pooled it
- Novel hydrazone compounds with broad-spectrum antiplasmodial activity and synergistic interactions with antimalarial drugs.Antimicrobial agents and chemotherapy · 2024Article
- Roles of Virtual Screening and Molecular Dynamics Simulations in Discovering and Understanding Antimalarial Drugs.International journal of molecular sciences · 2023Review
- Adipokinetic hormone signaling in the malaria vector Anopheles gambiae facilitates Plasmodium falciparum sporogony.Communications biology · 2023Article
- Rapid and Specific Action of Methylene Blue againstPharmaceutics · 2022Article
- Redox interactome in malaria parasite Plasmodium falciparum.Parasitology research · 2021Review
- Evaluation of Serum Interleukin 6, Tumor Necrosis Factor-Alpha, and Interferon-Gamma Levels in Relation to Body Mass Index and Blood Pressure in HIV Seropositive Pregnant Women Coinfected with Malaria.Interdisciplinary perspectives on infectious diseases · 2020Article
- Structure-Based Screening ofFrontiers in pharmacology · 2020Article
- Paraquat-Mediated Oxidative Stress inProteomes · 2018Article
- Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance.BMC genomics · 2017Article
- Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development.Free radical biology & medicine · 2016Article
- Glutathione-deficient Plasmodium berghei parasites exhibit growth delay and nuclear DNA damage.Free radical biology & medicine · 2016Article
- Potent Ex Vivo Activity of Naphthoquine and Methylene Blue against Drug-Resistant Clinical Isolates of Plasmodium falciparum and Plasmodium vivax.Antimicrobial agents and chemotherapy · 2015Article
- Role and Regulation of Glutathione Metabolism in Plasmodium falciparum.Molecules (Basel, Switzerland) · 2015Review
- Host reticulocytes provide metabolic reservoirs that can be exploited by malaria parasites.PLoS pathogens · 2015Article
- Genome-Wide Identification of the Target Genes of AP2-O, a Plasmodium AP2-Family Transcription Factor.PLoS pathogens · 2015Article
- Implications of Glutathione Levels in the Plasmodium berghei Response to Chloroquine and Artemisinin.PloS one · 2015Article
- Antimalarial action of artesunate involves DNA damage mediated by reactive oxygen species.Antimicrobial agents and chemotherapy · 2015Article
- The Plasmodium bottleneck: malaria parasite losses in the mosquito vector.Memorias do Instituto Oswaldo Cruz · 2014Article
- Cytostatic versus cytocidal profiling of quinoline drug combinations via modified fixed-ratio isobologram analysis.Malaria journal · 2013Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 3 countries.
Funding
Abstract
Malaria parasites contain a complete glutathione (GSH) redox system, and several enzymes of this system are considered potential targets for antimalarial drugs. Through generation of a gamma-glutamylcysteine synthetase (gamma-GCS)-null mutant of the rodent parasite Plasmodium berghei, we previously showed that de novo GSH synthesis is not critical for blood stage multiplication but is essential for oocyst development. In this study, phenotype analyses of mutant parasites lacking expression of glutathione reductase (GR) confirmed that GSH metabolism is critical for the mosquito oocyst stage. Similar to what was found for gamma-GCS, GR is not essential for blood stage growth. GR-null parasites showed the same sensitivity to methylene blue and eosin B as wild type parasites, demonstrating that these compounds target molecules other than GR in Plasmodium. Attempts to generate parasites lacking both GR and gamma-GCS by simultaneous disruption of gr and gamma-gcs were unsuccessful. This demonstrates that the maintenance of total GSH levels required for blood stage survival is dependent on either de novo GSH synthesis or glutathione disulfide (GSSG) reduction by Plasmodium GR. Our studies provide new insights into the role of the GSH system in malaria parasites with implications for the development of drugs targeting GSH metabolism.
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Registered trials
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