ArticleThe Journal of biological chemistry2015
Acetylation stimulates the epithelial sodium channel by reducing its ubiquitination and degradation.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 44 citations in OpenAlex.
- Research progress on lysine acetylation (Review).International journal of molecular medicine · 2026Review
- BDH1 acetylation at K116 modulates milk fat production in dairy goats.Journal of animal science and biotechnology · 2025Article
- Histone deacetylases and their inhibitors in kidney diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Review
- SECS, drugs, and Rac1&Rho: regulation of EnNaC in vascular endothelial cells.Pflugers Archiv : European journal of physiology · 2025Article
- Endothelial ENaC-α Restrains Oxidative Stress in Lung Capillaries in Murine Pneumococcal Pneumonia-associated Acute Lung Injury.American journal of respiratory cell and molecular biology · 2025Article
- Lysine acetylation of aquaporin-3 promotes water permeability but is not essential for urine concentrating ability.American journal of physiology. Renal physiology · 2025Article
- Endothelial ENaC as a repressor of oxidative stress and a guardian of lung capillary barrier function in bacterial and viral pneumonia.Frontiers in physiology · 2025Review
- Histone deacetylase expression following cisplatin-induced acute kidney injury in male and female mice.American journal of physiology. Renal physiology · 2024Article
- The cardioprotective role of sirtuins is mediated in part by regulating KAmerican journal of physiology. Cell physiology · 2023Article
- The Epithelial Sodium Channel-An Underestimated Drug Target.International journal of molecular sciences · 2023Review
- Histone deacetylase inhibitors (HDACi) increase expression of KCa2.3 (SK3) in primary microvascular endothelial cells.American journal of physiology. Cell physiology · 2022Article
- Paraoxonase 2 is an ER chaperone that regulates the epithelial NaAmerican journal of physiology. Cell physiology · 2022Article
- Deacetylation as a receptor-regulated direct activation switch for pannexin channels.Nature communications · 2021Article
- High salt intake induces collecting duct HDAC1-dependent NO signaling.American journal of physiology. Renal physiology · 2021Article
- Histone Deacetylases in Kidney Physiology and Acute Kidney Injury.Seminars in nephrology · 2020Review
- Review
- CBP mediated DOT1L acetylation confers DOT1L stability and promotes cancer metastasis.Theranostics · 2020Article
- Trichostatin A blocks aldosterone-induced NaBritish journal of pharmacology · 2019Article
- Dynamic changes in histone deacetylases following kidney ischemia-reperfusion injury are critical for promoting proximal tubule proliferation.American journal of physiology. Renal physiology · 2019Article
- Histone deacetylase inhibitor LMK235 attenuates vascular constriction and aortic remodelling in hypertension.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
The epithelial Na(+) channel (ENaC) functions as a pathway for Na(+) absorption in the kidney and lung, where it is crucial for Na(+) homeostasis and blood pressure regulation. ENaC is regulated in part through signaling pathways that control the ubiquitination state of ENaC lysines. A defect in ubiquitination causes Liddle syndrome, an inherited form of hypertension. Here we determined that α-, β-, and γENaC are also substrates for lysine acetylation. Trichostatin A (TSA), a histone deacetylase inhibitor, enhanced ENaC acetylation and increased ENaC abundance in the total cell lysate and at the cell surface. Moreover, TSA increased ENaC current in Fischer rat thyroid and kidney collecting duct epithelia. We found that HDAC7 is expressed in the kidney collecting duct, supporting a potential role for this histone deacetylase in ENaC regulation. HDAC7 overexpression reduced ENaC abundance and ENaC current, whereas ENaC abundance and current were increased by silencing of HDAC7. ENaC and HDAC7 form a complex, as detected by coimmunoprecipitation. We observed a reciprocal relationship between acetylation and ubiquitination; TSA reduced ENaC ubiquitination, whereas HDAC7 increased ubiquitination. By reducing ENaC ubiquitination, TSA decreased the rate of ENaC degradation. Thus, acetylation increases epithelial Na(+) absorption by antagonizing ENaC ubiquitination. This stabilizes ENaC, and hence, increases its abundance at the cell surface.
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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.