ArticleAntimicrobial agents and chemotherapy2002
Relationship between chloroquine toxicity and iron acquisition in Saccharomyces cerevisiae.
Article in Antimicrobial agents and chemotherapy, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- The possible mechanisms of action of 4-aminoquinolines (chloroquine/hydroxychloroquine) against Sars-Cov-2 infection (COVID-19): A role for iron homeostasis?Pharmacological research · 2020Review
- Synergistic activity of chloroquine with fluconazole against fluconazole-resistant isolates of Candida species.Antimicrobial agents and chemotherapy · 2015Article
- The effect of antibacterial and non-antibacterial compounds alone or associated with antifugals upon fungi.Frontiers in microbiology · 2015Review
- Essential functions of iron-requiring proteins in DNA replication, repair and cell cycle control.Protein & cell · 2014Review
- Signaling of chloroquine-induced stress in the yeast Saccharomyces cerevisiae requires the Hog1 and Slt2 mitogen-activated protein kinase pathways.Antimicrobial agents and chemotherapy · 2014Article
- Repeat polymorphisms in the low-complexity regions of Plasmodium falciparum ABC transporters and associations with in vitro antimalarial responses.Antimicrobial agents and chemotherapy · 2013Article
- Reply to "chloroquine, an antifungal but also a fertility drug".Antimicrobial agents and chemotherapy · 2013Article
- Iron economy in Chlamydomonas reinhardtii.Frontiers in plant science · 2013Review
- Yeast toxicogenomics: genome-wide responses to chemical stresses with impact in environmental health, pharmacology, and biotechnology.Frontiers in genetics · 2012Article
- Discovering thiamine transporters as targets of chloroquine using a novel functional genomics strategy.PLoS genetics · 2012Article
- A genome-wide screen identifies yeast genes required for protection against or enhanced cytotoxicity of the antimalarial drug quinine.Molecular genetics and genomics : MGG · 2011Article
- Transcriptomic profiling of the Saccharomyces cerevisiae response to quinine reveals a glucose limitation response attributable to drug-induced inhibition of glucose uptake.Antimicrobial agents and chemotherapy · 2009Article
- Sitamaquine sensitivity in Leishmania species is not mediated by drug accumulation in acidocalcisomes.Antimicrobial agents and chemotherapy · 2008Article
- Genomewide expression profiling of cryptolepine-induced toxicity in Saccharomyces cerevisiae.Antimicrobial agents and chemotherapy · 2008Article
- Chloroquine sensitizes biofilms of Candida albicans to antifungal azoles.The Brazilian journal of infectious diseases : an official publication of the Brazilian Society of Infectious DiseasesArticle
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
Chloroquine is one of the most effective antimalarials, but resistance to it is becoming widespread. However, we do not fully understand either the drug's mode of action or the mechanism of resistance. In an effort to expand our understanding of the mechanism of action and resistance associated with chloroquine, we used Saccharomyces cerevisiae as a model eukaryotic system. To aid in the discovery of potential drug targets we applied the transcriptional profiling method to identify genes transcriptionally responsive to chloroquine treatment in S. cerevisiae. Among the genes that were differentially expressed with chloroquine treatment were a number of metal transporters involved in iron acquisition (SIT1, ARN2, ARN4, and SMF2). These genes exhibit similar expression patterns, and several are known to be regulated by AFT1, a DNA binding protein, which responds to iron levels in the cell. We investigated the role of chloroquine in iron metabolism by using a variety of approaches, including pharmacological, genetic, and biochemical techniques. For these experiments, we utilized yeast lacking the major iron uptake pathways (FET3 and FET4) and yeast deficient in SIT1, encoding the major up-regulated iron siderophore transporter. Our experiments show that yeast genetically or environmentally limited in iron availability has increased sensitivity to chloroquine in pharmacological assays and that the addition of iron rescues these cells from chloroquine killing. 55FeCl3 accumulation was inhibited in the presence of chloroquine, and kinetic analysis demonstrated that inhibition was competitive. These results are consistent with deprivation of iron as a mechanism of chloroquine killing in yeast.
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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.