ReviewThe Biochemical journal2012
Cell signalling by reactive lipid species: new concepts and molecular mechanisms.
Review in The Biochemical journal, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 140 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
140 citing papers in PubMed, 306 citations in OpenAlex.
- The Phase 3 INVIGORATE Trial of Reproxalap in Patients with Seasonal Allergic Conjunctivitis.Clinical ophthalmology (Auckland, N.Z.) · 2023Trial
- A Randomized Double-Masked Phase 2a Trial to Evaluate Activity and Safety of Topical Ocular Reproxalap, a Novel RASP Inhibitor, in Dry Eye Disease.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2021Trial
- Randomized Phase 2 Trial of Reproxalap, a Novel Reactive Aldehyde Species Inhibitor, in Patients with Noninfectious Anterior Uveitis: Model for Corticosteroid Replacement.Journal of ocular pharmacology and therapeutics : the official journal of the Association for Ocular Pharmacology and Therapeutics · 2020Trial
- Molecular Mechanisms and Network Integration of Oxylipin Signaling in Plant Abiotic Stress Tolerance.International journal of molecular sciences · 2026Review
- The Oxidative Stress and Inflammatory Metabolic Pathways of Some Environmental Toxicants Inflicting Human Disorders.Toxics · 2026Review
- Precision Covalent Drug Discovery Inspired by Endogenous Electrophilic Signalling in Immune Cells.Biomedicines · 2026Article
- The role of ferroptosis in the pathogenesis and treatment of breast cancer.Journal of translational medicine · 2026Review
- Reproxalap - A Novel Treatment Option for Allergic Conjunctivitis - A Comprehensive Narrative Review.Health science reports · 2026Article
- Combination of sodium pentaborate pentahydrate, curcumin and piperine treatment induces ferroptosis in hepatocellular carcinoma cells by regulating iron homeostasis and ROS activity in vitro.Medical oncology (Northwood, London, England) · 2026Article
- Yin-Dan-Ping-Gan Capsule Mitigates CCLPharmaceuticals (Basel, Switzerland) · 2026Article
- Neuroprotective Effects ofArchives of Razi Institute · 2025Article
- Reproxalap in patients with seasonal allergic conjunctivitis: a systematic review and meta-analysis.Journal of ophthalmic inflammation and infection · 2025Review
- The Role of Oxidative Stress-Induced Senescence in the Pathogenesis of Preeclampsia.Antioxidants (Basel, Switzerland) · 2025Review
- A systematical review on traditional Chinese medicine treating chronic diseases via regulating ferroptosis from the perspective of experimental evidence and clinical application.Chinese herbal medicines · 2025Review
- Interplay between lipid dysregulation and ferroptosis in chondrocytes and the targeted therapy effect of metformin on osteoarthritis.Journal of advanced research · 2025Article
- Comprehensive analysis of the effects of high stocking density stress on broiler health.Frontiers in veterinary science · 2025Review
- P53 Regulation upon Lipid Peroxidation and Ferroptosis for Intervention against Atherogenesis.Current medicinal chemistry · 2025Review
- Iron and Cell Death.Advances in experimental medicine and biology · 2025Review
- Plasmalogen oxidation induces the generation of excited molecules and electrophilic lipid species.PNAS nexus · 2024Article
- Heavy metals, oxidative stress, and the role of AhR signaling.Toxicology and applied pharmacology · 2024Review
80 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The process of lipid peroxidation is widespread in biology and is mediated through both enzymatic and non-enzymatic pathways. A significant proportion of the oxidized lipid products are electrophilic in nature, the RLS (reactive lipid species), and react with cellular nucleophiles such as the amino acids cysteine, lysine and histidine. Cell signalling by electrophiles appears to be limited to the modification of cysteine residues in proteins, whereas non-specific toxic effects involve modification of other nucleophiles. RLS have been found to participate in several physiological pathways including resolution of inflammation, cell death and induction of cellular antioxidants through the modification of specific signalling proteins. The covalent modification of proteins endows some unique features to this signalling mechanism which we have termed the 'covalent advantage'. For example, covalent modification of signalling proteins allows for the accumulation of a signal over time. The activation of cell signalling pathways by electrophiles is hierarchical and depends on a complex interaction of factors such as the intrinsic chemical reactivity of the electrophile, the intracellular domain to which it is exposed and steric factors. This introduces the concept of electrophilic signalling domains in which the production of the lipid electrophile is in close proximity to the thiol-containing signalling protein. In addition, we propose that the role of glutathione and associated enzymes is to insulate the signalling domain from uncontrolled electrophilic stress. The persistence of the signal is in turn regulated by the proteasomal pathway which may itself be subject to redox regulation by RLS. Cell death mediated by RLS is associated with bioenergetic dysfunction, and the damaged proteins are probably removed by the lysosome-autophagy pathway.
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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.