ReviewToxicology and applied pharmacology2015
Antioxidant role of glutathione S-transferases: 4-Hydroxynonenal, a key molecule in stress-mediated signaling.
Review in Toxicology and applied pharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 117 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
117 citing papers in PubMed, 1 synthesis or guideline pooled it, 230 citations in OpenAlex.
- Antioxidant enzymes, oxidative stress, and physiological aging markers in Drosophila melanogaster (Diptera: Drosophilidae): a systematic review with translational perspectives.Journal of insect science (Online) · 2026Pooled it
- Dual Compartmentalization of GSTA4 Suppresses Ferroptosis to Drive Antiandrogen Resistance in Prostate Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Chlorogenic acid attenuates LPS-induced hepatic oxidative stress in broilers by regulating cyclooxygenase-2 expression.Poultry science · 2026Article
- Effects of High-Dextrose Intake on the Structural and Functional Properties of the Small Intestine in Young-Maturing and Middle-Aged Rats.International journal of molecular sciences · 2026Article
- Mitochondrial vulnerability to aldehydic load and the role mitochondrial aldehyde dehydrogenases.Pharmacological research · 2026Review
- GSH-Related Enzymes GPx4, Chac1, and GSTs and Redox Regulation of Ferroptosis in Cancer.International journal of molecular sciences · 2026Review
- Exploring mechanisms of scar-free skin wound healing in adult zebrafish in comparison to mouse.PLoS genetics · 2026Article
- Liposomal Myricetin Nanoantioxidants Attenuate Methotrexate-Induced Hepatotoxicity by Modulating Oxidative Stress, Inflammation, and Apoptosis in Rats.Antioxidants (Basel, Switzerland) · 2026Article
- Oxeiptosis - potential in cancer treatment?Expert reviews in molecular medicine · 2026Review
- Proteomic analysis reveals shared biological pathways linking acrolein to biomolecular changes in the acute phase of rat spinal cord injury.bioRxiv : the preprint server for biology · 2026Article
- Reserpine prolongs lifespan but compromises locomotion and heat-stress resilience in Drosophila melanogaster.npj aging · 2026Article
- Single-Cell Analysis Delineates Glutathione Metabolism-Related Gene Signatures in the Glioblastoma Microenvironment and Identifies GSTA4 as a Regulator of Malignant Behaviors.International journal of genomics · 2026Article
- Gastrodin extends the lifespan of Caenorhabditis elegans via the DAF-16/FOXO signaling pathway and autophagy.Functional & integrative genomics · 2025Article
- Extracellular Matrix Microstructures Directly Regulate Glutathione Bioavailability in Human Hepatocytes.Biomacromolecules · 2025Article
- Plasma 4-hydroxynonenal estimates severity and prognosis in patients with acute exacerbation of chronic obstructive pulmonary disease.Scientific reports · 2025Article
- Linalool May Exert Neuroprotective Effects Against Cadmium-Induced Hippocampal Neurodegeneration by Regulating the 4-HNE/NF-κB Signaling Pathway.Biological trace element research · 2025Article
- Comparative Proteomic Characterization of Serum-Free Cultivated HepG2 Cells Reveals Upregulated Drug Metabolism and Increased Oxidative Stress Protection.Journal of proteome research · 2025Article
- Genetic Interactions of Phase II Xenobiotic-Metabolizing EnzymesJournal of xenobiotics · 2025Article
- Genome-Wide Identification and Drought-Responsive Functional Analysis of theAntioxidants (Basel, Switzerland) · 2025Article
- Methylglyoxal Formation-Metabolic Routes and Consequences.Antioxidants (Basel, Switzerland) · 2025Review
57 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
6 authors at 4 institutions in 1 country.
Funding
Abstract
4-Hydroxy-2-trans-nonenal (4HNE), one of the major end products of lipid peroxidation (LPO), has been shown to induce apoptosis in a variety of cell lines. It appears to modulate signaling processes in more than one way because it has been suggested to have a role in signaling for differentiation and proliferation. It has been known that glutathione S-transferases (GSTs) can reduce lipid hydroperoxides through their Se-independent glutathione-peroxidase activity and that these enzymes can also detoxify LPO end-products such as 4HNE. Available evidence from earlier studies together with results of recent studies in our laboratories strongly suggests that LPO products, particularly hydroperoxides and 4HNE, are involved in the mechanisms of stress-mediated signaling and that it can be modulated by the alpha-class GSTs through the regulation of the intracellular concentrations of 4HNE. We demonstrate that 4HNE induced apoptosis in various cell lines is accompanied with c-Jun-N-terminal kinase (JNK) and caspase-3 activation. Cells exposed to mild, transient heat or oxidative stress acquire the capacity to exclude intracellular 4HNE at a faster rate by inducing GSTA4-4 which conjugates 4HNE to glutathione (GSH), and RLIP76 which mediates the ATP-dependent transport of the GSH-conjugate of 4HNE (GS-HNE). The balance between formation and exclusion promotes different cellular processes - higher concentrations of 4HNE promote apoptosis; whereas, lower concentrations promote proliferation. In this article, we provide a brief summary of the cellular effects of 4HNE, followed by a review of its GST-catalyzed detoxification, with an emphasis on the structural attributes that play an important role in the interactions with alpha-class GSTA4-4. Taken together, 4HNE is a key signaling molecule and that GSTs being determinants of its intracellular concentrations, can regulate stress-mediated signaling, are reviewed in this article.
Indexed as
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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.