ArticleProceedings of the National Academy of Sciences of the United States of America2015
Glutathione and multidrug resistance protein transporter mediate a self-propelled disposal of bismuth in human cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 76 citations in OpenAlex.
- ABCC1 promotes GSH-dependent iron transport and resistance to Fe(II) and Cu(II) chelators.Biometals : an international journal on the role of metal ions in biology, biochemistry, and medicine · 2025Article
- Bismuth subsalicylate profoundly alters gut microbiome and immunity with increased susceptibility to infection.medRxiv : the preprint server for health sciences · 2025Article
- Ligand supplementation restores the cancer therapy efficacy of the antirheumatic drug auranofin from serum inactivation.Nature communications · 2025Article
- Panoramic lead-immune system interactome reveals diversified mechanisms of immunotoxicity upon chronic lead exposure.Cell biology and toxicology · 2025Article
- Bismuth-Cyclized Cell-Penetrating Peptides.Molecular pharmaceutics · 2024Article
- Bismuth-based drugs sensitize Pseudomonas aeruginosa to multiple antibiotics by disrupting iron homeostasis.Nature microbiology · 2024Article
- Biodegradable Poly(amino acid)-Bismuth Nanotheranostic Agents for CT/MR Imaging and Photothermal-Chemodynamic Synergistic Therapy.Chem & bio engineering · 2024Article
- Clinically used drug arsenic trioxide targets XIAP and overcomes apoptosis resistance in an organoid-based preclinical cancer model.Chemical science · 2024Article
- Copper regulates the host innate immune response against bacterial infection via activation of ALPK1 kinase.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Article
- Dual-action gallium-flavonoid compounds for combatingRSC chemical biology · 2023Article
- Biological Activities of Bismuth Compounds: An Overview of the New Findings and the Old Challenges Not Yet Overcome.Molecules (Basel, Switzerland) · 2023Review
- Computed Tomography of Cartilage: An Exploration of Novel Cationic Bismuth Contrast Agent.Annals of biomedical engineering · 2023Article
- Bismuth Drugs Reverse Tet(X)-Conferred Tigecycline Resistance in Gram-Negative Bacteria.Microbiology spectrum · 2022Article
- Orally administered bismuth drug together withChemical science · 2022Article
- Bismuth Reduces Cisplatin-Induced NephrotoxicityFrontiers in pharmacology · 2022Article
- Glutathione-coordinated metal complexes as substrates for cellular transporters.Metallomics : integrated biometal science · 2021Review
- Defining the mechanism of the mitochondrial Atm1p [2Fe-2S] cluster exporter.Metallomics : integrated biometal science · 2020Article
- Bismuth Porphyrin Antagonizes Cisplatin-Induced Nephrotoxicity via Unexpected Metallothionein-Independent Mechanisms.iScience · 2020Article
- Metal Complexes, an Untapped Source of Antibiotic Potential?Antibiotics (Basel, Switzerland) · 2020Article
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Authors and funding
4 authors at 1 institution in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Glutathione and multidrug resistance protein (MRP) play an important role on the metabolism of a variety of drugs. Bismuth drugs have been used to treat gastrointestinal disorder and Helicobacter pylori infection for decades without exerting acute toxicity. They were found to interact with a wide variety of biomolecules, but the major metabolic pathway remains unknown. For the first time (to our knowledge), we systematically and quantitatively studied the metabolism of bismuth in human cells. Our data demonstrated that over 90% of bismuth was passively absorbed, conjugated to glutathione, and transported into vesicles by MRP transporter. Mathematical modeling of the system reveals an interesting phenomenon. Passively absorbed bismuth consumes intracellular glutathione, which therefore activates de novo biosynthesis of glutathione. Reciprocally, sequestration by glutathione facilitates the passive uptake of bismuth and thus completes a self-sustaining positive feedback circle. This mechanism robustly removes bismuth from both intra- and extracellular space, protecting critical systems of human body from acute toxicity. It elucidates the selectivity of bismuth drugs between human and pathogens that lack of glutathione, such as Helicobacter pylori, opening new horizons for further drug development.
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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.