ArticleNature communications2015
Leukotriene C4 is the major trigger of stress-induced oxidative DNA damage.
Article in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
60 citing papers in PubMed, 106 citations in OpenAlex.
- Oral Recombinant Human Collagen III Protects Gastric Mucosa via G-Quadruplex-Mediated Activation of the Pla2g4a-Prostaglandin Axis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Effects of DietaryAnimals : an open access journal from MDPI · 2026Article
- Molecular mechanisms and recent advances in cellular senescence.Cell & bioscience · 2026Review
- Integrative systems biology analysis reveals diagnostic and prognostic DNA methylation signatures in esophageal cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- Fluorescence-Guided Spatial Mapping of p21-Expressing Senescent Cells in Aged Liver at Single-Cell Resolution.Biomolecules · 2026Article
- Single-atom Pt doped nanoceria for enhanced cell phagocytosis and nanozyme activities in keratitis immune regulation.Journal of nanobiotechnology · 2026Article
- Health-enhancing physical activity induce beneficial skeletal muscle mitochondrial adaptations in individuals with rheumatoid arthritis.Clinical rheumatology · 2025Article
- The role of glutathione S-transferases in human disease pathogenesis and their current inhibitors.Genes & diseases · 2025Review
- Article
- Microglial repopulation reverses radiation-induced cognitive dysfunction by restoring medial prefrontal cortex activity and modulating leukotriene-C4 synthesis.Acta neuropathologica communications · 2025Article
- Structure Bioinformatics of Six Human Integral Transmembrane Enzymes and their AlphaFold3 Predicted Water-Soluble QTY Analogs: Insights into FACE1 and STEA4 Binding Mechanisms.Pharmaceutical research · 2025Article
- Article
- Cysteinyl leukotriene receptor 1 regulates cellular glucose levels in human retinal cells.Molecular vision · 2025Article
- In Silico Analysis of Non-Conventional Oxidative Stress-Related Enzymes and Their Potential Relationship with Carcinogenesis.Antioxidants (Basel, Switzerland) · 2024Article
- The role of signaling pathways mediated by the GPCRs CysLTR1/2 in melanocyte proliferation and senescence.Science signaling · 2024Review
- Myocardial reperfusion injury exacerbation due to ALDH2 deficiency is mediated by neutrophil extracellular traps and prevented by leukotriene C4 inhibition.European heart journal · 2024Article
- The role of human 5-Lipoxygenase (5-LO) in carcinogenesis - a question of canonical and non-canonical functions.Oncogene · 2024Review
- Morphometric Analysis of the Eye by Magnetic Resonance Imaging inBiomedicines · 2024Article
- Implications of DNA damage in chronic lung disease.Frontiers in cell and developmental biology · 2024Review
- Metabolome and transcriptome integration reveals cerebral cortical metabolic profiles in rats with subarachnoid hemorrhage.Frontiers in aging neuroscience · 2024Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress and major chemotherapeutic agents damage DNA by generating reactive oxygen species (ROS). Here we show that ER stress and chemotherapy induce leukotriene C4 (LTC4) biosynthesis by transcriptionally upregulating and activating the enzyme microsomal glutathione-S-transferase 2 (MGST2) in cells of non-haematopoietic lineage. ER stress and chemotherapy also trigger nuclear translocation of the two LTC4 receptors. Acting in an intracrine manner, LTC4 then elicits nuclear translocation of NADPH oxidase 4 (NOX4), ROS accumulation and oxidative DNA damage. Mgst2 deficiency, RNAi and LTC4 receptor antagonists abolish ER stress- and chemotherapy-induced ROS and oxidative DNA damage in vitro and in mouse kidneys. Cell death and mouse morbidity are also significantly attenuated. Hence, MGST2-generated LTC4 is a major mediator of ER stress- and chemotherapy-triggered oxidative stress and oxidative DNA damage. LTC4 inhibitors, commonly used for asthma, could find broad clinical use in major human pathologies associated with ER stress-activated NOX4.
Indexed as
Identifiers
What 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.