ArticleBlood advances2017
The lipid peroxidation product 4-hydroxy-2-nonenal induces tissue factor decryption via ROS generation and the thioredoxin system.
Article in Blood advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 37 citations in OpenAlex.
- Exploring the Interplay of Antioxidants, Inflammation, and Oxidative Stress: Mechanisms, Therapeutic Potential, and Clinical Implications.Diseases (Basel, Switzerland) · 2025Review
- Impact of tissue factor expression and administration routes on thrombosis development induced by mesenchymal stem/stromal cell infusions: re-evaluating the dogma.Stem cell research & therapy · 2024Article
- Targeting Cysteine Oxidation in Thrombotic Disorders.Antioxidants (Basel, Switzerland) · 2024Review
- Tissue factor in cancer-associated thromboembolism: possible mechanisms and clinical applications.British journal of cancer · 2022Review
- Molecular mechanisms of ferroptosis and the potential therapeutic targets of ferroptosis signaling pathways for glioblastoma.Frontiers in pharmacology · 2022Review
- Bacitracin and Rutin Regulate Tissue Factor Production in Inflammatory Monocytes and Acute Myeloid Leukemia Blasts.Cancers · 2021Article
- Lidocaine Alleviates Sepsis-Induced Acute Lung Injury in Mice by Suppressing Tissue Factor and Matrix Metalloproteinase-2/9.Oxidative medicine and cellular longevity · 2021Article
- Oxidative Stress Product, 4-Hydroxy-2-Nonenal, Induces the Release of Tissue Factor-Positive Microvesicles From Perivascular Cells Into Circulation.Arteriosclerosis, thrombosis, and vascular biology · 2021Article
- Factors Affecting the Formation and Treatment of Thrombosis by Natural and Synthetic Compounds.International journal of molecular sciences · 2020Review
- Oxidized Perilla and Linseed Oils Induce Neuronal Apoptosis by Caspase-Dependent and -Independent Pathways.Foods (Basel, Switzerland) · 2020Article
- The procoagulant activity of tissue factor expressed on fibroblasts is increased by tissue factor-negative extracellular vesicles.PloS one · 2020Article
- Vasodilator oxyfedrine inhibits aldehyde metabolism and thereby sensitizes cancer cells to xCT-targeted therapy.Cancer science · 2020Article
- Platelet P-selectin triggers rapid surface exposure of tissue factor in monocytes.Scientific reports · 2019Article
- Role of Cell Surface Lipids and Thiol-Disulphide Exchange Pathways in Regulating the Encryption and Decryption of Tissue Factor.Thrombosis and haemostasis · 2019Review
- Paraoxonases Activities and Polymorphisms in Elderly and Old-Age Diseases: An Overview.Antioxidants (Basel, Switzerland) · 2019Review
- Effectors of thioredoxin reductase: Brevetoxins and manumycin-A.Comparative biochemistry and physiology. Toxicology & pharmacology : CBP · 2019Article
- Alcohol Dehydrogenase 1B Suppresses β-Amyloid-Induced Neuron Apoptosis.Frontiers in aging neuroscience · 2019Article
- Anti-GPC3 antibody-modified sorafenib-loaded nanoparticles significantly inhibited HepG2 hepatocellular carcinoma.Drug delivery · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Many pathophysiologic agents transform cryptic tissue factor (TF) on cells to prothrombotic TF, and one such stimulus is 4-hydroxy-2-nonenal (HNE), the most abundant aldehyde produced by the oxidation of ω-6 polyunsaturated fatty acids. HNE was shown to induce reactive oxygen species (ROS) generation and p38 MAPK activation, but the link between them and their role in TF decryption are unclear. The present study was carried out to elucidate potential mechanisms involved in HNE-induced TF decryption in monocytic cells. The data presented herein show that mitochondria are the primary source for HNE-induced ROS generation. The inhibition of mitochondrial electron transport chain complex III and V blocked HNE-induced ROS generation, but not p38 MAPK activation. These inhibitors reduced phosphatidylserine (PS) externalization and TF decryption significantly, but not completely. HNE treatment inhibited the activities of thioredoxin reductase (TrxR) and thioredoxin (Trx), independent of ROS. Inhibition of the TrxR/Trx system by HNE or pharmacological inhibitors induced p38 MAPK activation, PS externalization, and TF decryption. Additional studies revealed that the inhibition of TrxR/Trx led to activation of apoptosis signal-regulating kinase (ASK-1) and mitogen-activated protein kinase kinase 3/6. Inhibition of ASK-1 expression by small interfering RNA or its activity by pharmacological inhibitors diminished HNE-induced TF decryption. Overall, our data suggest that HNE induces TF decryption by 2 distinctive pathways. One is ROS dependent but independent of p38 MAPK activation, and the other is via TrxR/Trx and is p38 MAPK activation dependent. However, both mechanisms result in the enhancement of PS at the outer leaflet that is responsible for TF decryption.
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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.