ArticleFrontiers in pharmacology2014
Inhibiting lung lining fluid glutathione metabolism with GGsTop as a novel treatment for asthma.
Article in Frontiers in pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 41 citations in OpenAlex.
- The genetic architecture of pneumonia susceptibility implicates mucin biology and a relationship with psychiatric illness.Nature communications · 2022Pooled it
- Bioresponsive engineered nanoparticles for immunomodulation.BMC medicine · 2025Review
- Marine-Inspired Ovothiol Analogs Inhibit Membrane-Bound Gamma-Glutamyl-Transpeptidase and Modulate Reactive Oxygen Species and Glutathione Levels in Human Leukemic Cells.Marine drugs · 2025Article
- Serum γ-glutamyl transferase as a novel risk indicator for lung cancer: insights from four million Koreans.Respiratory research · 2025Article
- Gamma-glutamyl transferase and risk of all-cause and disease-specific mortality: a nationwide cohort study.Scientific reports · 2023Article
- Inhibition of γ-glutamyl transferase suppresses airway hyperresponsiveness and airway inflammation in a mouse model of steroid resistant asthma exacerbation.Frontiers in immunology · 2023Article
- Design and evaluation of novel analogs of 2-amino-4-boronobutanoic acid (ABBA) as inhibitors of human gamma-glutamyl transpeptidase.Bioorganic & medicinal chemistry · 2022Article
- Metabolomic Associations of Asthma in the Hispanic Community Health Study/Study of Latinos.Metabolites · 2022Article
- Heme Peroxidases at Unperturbed and Inflamed Mucous Surfaces.Antioxidants (Basel, Switzerland) · 2021Review
- Inhibition of γ-glutamyltransferase ameliorates ischaemia-reoxygenation tissue damage in rats with hepatic steatosis.British journal of pharmacology · 2020Article
- Endoplasmic reticulum stress and glutathione therapeutics in chronic lung diseases.Redox biology · 2020Review
- Dysregulation of the glutaredoxin/American journal of physiology. Cell physiology · 2020Article
- Probing the Interactions of Sulfur-Containing Histidine Compounds with Human Gamma-Glutamyl Transpeptidase.Marine drugs · 2019Article
- Sulfur-containing histidine compounds inhibit γ-glutamyl transpeptidase activity in human cancer cells.The Journal of biological chemistry · 2019Article
- Structure of 6-diazo-5-oxo-norleucine-bound human gamma-glutamyl transpeptidase 1, a novel mechanism of inactivation.Protein science : a publication of the Protein Society · 2017Article
- Human γ-Glutamyl Transpeptidase 1: STRUCTURES OF THE FREE ENZYME, INHIBITOR-BOUND TETRAHEDRAL TRANSITION STATES, AND GLUTAMATE-BOUND ENZYME REVEAL NOVEL MOVEMENT WITHIN THE ACTIVE SITE DURING CATALYSIS.The Journal of biological chemistry · 2015Article
- Editorial: the changing faces of glutathione, a cellular protagonist.Frontiers in pharmacology · 2015Article
- Effects of GGsTopIn vivo (Athens, Greece)Article
- Crystal structures of glutathione- and inhibitor-bound human GGT1: critical interactions within the cysteinylglycine binding site.The Journal of biological chemistryArticle
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 3 countries.
Funding
Abstract
Asthma is characterized by airway inflammation. Inflammation is associated with oxidant stress. Airway epithelial cells are shielded from this stress by a thin layer of lung lining fluid (LLF) which contains an abundance of the antioxidant glutathione. LLF glutathione metabolism is regulated by γ-glutamyl transferase (GGT). Loss of LLF GGT activity in the mutant GGT(enu1) mouse causes an increase in baseline LLF glutathione content which is magnified in an IL-13 model of allergic airway inflammation and protective against asthma. Normal mice are susceptible to asthma in this model but can be protected with acivicin, a GGT inhibitor. GGT is a target to treat asthma but acivicin toxicity limits clinical use. GGsTop is a novel GGT inhibitor. GGsTop inhibits LLF GGT activity only when delivered through the airway. In the IL-13 model, mice treated with IL-13 and GGsTop exhibit a lung inflammatory response similar to that of mice treated with IL-13 alone. But mice treated with IL-13 and GGsTop show attenuation of methacholine-stimulated airway hyper-reactivity, inhibition of Muc5ac and Muc5b gene induction, decreased airway epithelial cell mucous accumulation and a fourfold increase in LLF glutathione content compared to mice treated with IL-13 alone. Mice treated with GGsTop alone are no different from that of mice treated with saline alone, and show no signs of toxicity. GGsTop could represent a valuable pharmacological tool to inhibit LLF GGT activity in pulmonary disease models. The associated increase in LLF glutathione can protect lung airway epithelial cells against oxidant injury associated with inflammation in asthma.
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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.