ArticleScientific reports2016
Secreted APE1/Ref-1 inhibits TNF-α-stimulated endothelial inflammation via thiol-disulfide exchange in TNF receptor.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 36 citations in OpenAlex.
- Ref-1 redox activity modulates canonical Wnt signaling in endothelial cells.Redox biology · 2025Article
- Aspirin-induced acetylation of APE1/Ref-1 enhances RAGE binding and promotes apoptosis in ovarian cancer cells.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- RNA-seq analysis reveals key genes associated with downregulation of APE1 in esophageal squamous cell carcinoma.Frontiers in genetics · 2025Article
- Protective effect of secretory APE1/Ref-1 on doxorubicin-induced cardiotoxicity via suppression of ROS and p53 pathway.ESC heart failure · 2024Article
- Apurinic/apyrimidinic endonuclease 1 alleviates inflammation in fibroblast-like synoviocytes from patients with rheumatoid arthritis.Central-European journal of immunology · 2024Article
- Dual Function of Secreted APE1/Ref-1 in TNBC Tumorigenesis: An Apoptotic Initiator and a Regulator of Chronic Inflammatory Signaling.International journal of molecular sciences · 2022Article
- APE1/Ref-1 Role in Inflammation and Immune Response.Frontiers in immunology · 2022Review
- Vitexin inhibits APEX1 to counteract the flow-induced endothelial inflammation.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Elevated APE1/Ref-1 Levels of Synovial Fluids in Patients with Rheumatoid Arthritis: Reflection of Disease Activity.Journal of clinical medicine · 2021Article
- Inhibition of APE1/Ref-1 for Neovascular Eye Diseases: From Biology to Therapy.International journal of molecular sciences · 2021Review
- 17Biomedicines · 2021Article
- Ref-1 protects against FeClThe Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- New Horizons for the Roles and Association of APE1/Ref-1 and ABCA1 in Atherosclerosis.Journal of inflammation research · 2021Review
- Plasma APE1/Ref-1 Correlates with Atherosclerotic Inflammation in ApoEBiomedicines · 2020Article
- Embryonic stem cell extracts improve wound healing in diabetic mice.Acta diabetologica · 2020Article
- Review
- Evolution, role in inflammation, and redox control of leaderless secretory proteins.The Journal of biological chemistry · 2020Review
- The Biological Role of Apurinic/Apyrimidinic Endonuclease1/Redox Factor-1 as a Therapeutic Target for Vascular Inflammation and as a Serologic Biomarker.Biomedicines · 2020Review
- APE1 inhibits foam cell formation from macrophages via LOX1 suppression.American journal of translational research · 2020Article
- ATP Binding Cassette Transporter A1 is Involved in Extracellular Secretion of Acetylated APE1/Ref-1.International journal of molecular sciences · 2019Article
Corrections and comments
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Apurinic apyrimidinic endonuclease 1/Redox factor-1 (APE1/Ref-1) is a multifunctional protein with redox activity and is proved to be secreted from stimulated cells. The aim of this study was to evaluate the functions of extracellular APE1/Ref-1 with respect to leading anti-inflammatory signaling in TNF-α-stimulated endothelial cells in response to acetylation. Treatment of TNF-α-stimulated endothelial cells with an inhibitor of deacetylase that causes intracellular acetylation, considerably suppressed vascular cell adhesion molecule-1 (VCAM-1). During TSA-mediated acetylation in culture, a time-dependent increase in secreted APE1/Ref-1 was confirmed. The acetyl moiety of acetylated-APE1/Ref-1 was rapidly removed based on the removal kinetics. Additionally, recombinant human (rh) APE1/Ref-1 with reducing activity induced a conformational change in rh TNF-α receptor 1 (TNFR1) by thiol-disulfide exchange. Following treatment with the neutralizing anti-APE1/Ref-1 antibody, inflammatory signals via the binding of TNF-α to TNFR1 were remarkably recovered, leading to up-regulation of reactive oxygen species generation and VCAM-1, in accordance with the activation of p66(shc) and p38 MAPK. These results strongly indicate that anti-inflammatory effects in TNF-α-stimulated endothelial cells by acetylation are tightly linked to secreted APE1/Ref-1, which inhibits TNF-α binding to TNFR1 by reductive conformational change, with suggestion as an endogenous inhibitor of vascular inflammation.
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