ArticleAmerican journal of respiratory cell and molecular biology2014
Novel mechanism of attenuation of LPS-induced NF-κB activation by the heat shock protein 90 inhibitor, 17-N-allylamino-17-demethoxygeldanamycin, in human lung microvascular endothelial cells.
Article in American journal of respiratory cell and molecular biology, 2014. 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, 33 citations in OpenAlex.
- Beyond Folding: Expanding the Functional Landscape of Hsp90 Chaperone Machinery in Health and Disease.International journal of molecular sciences · 2025Review
- Involvement of NEK2 and NEK9 in LPS - induced endothelial barrier dysfunction.Microvascular research · 2024Article
- The deubiquitinase USP40 preserves endothelial integrity by targeting the heat shock protein HSP90β.Experimental & molecular medicine · 2024Article
- HSP90β promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling.Cell death and differentiation · 2023Article
- Targeting HIF-1α by Natural and Synthetic Compounds: A Promising Approach for Anti-Cancer Therapeutics Development.Molecules (Basel, Switzerland) · 2022Review
- Article
- HSP90 Inhibitors Modulate SARS-CoV-2 Spike Protein Subunit 1-Induced Human Pulmonary Microvascular Endothelial Activation and Barrier Dysfunction.Frontiers in physiology · 2022Article
- Nanotherapeutics in the treatment of acute respiratory distress syndrome.Life sciences · 2021Review
- Article
- Hsp90 inhibition protects the brain microvascular endothelium against oxidative stress.Brain disorders (Amsterdam, Netherlands) · 2021Article
- P23 Acts as Functional RBP in the Macrophage Inflammation Response.Frontiers in molecular biosciences · 2021Article
- SIRT2 suppresses expression of inflammatory factors via Hsp90-glucocorticoid receptor signalling.Journal of cellular and molecular medicine · 2020Article
- Histone Deacetylases (HDACs) and Atherosclerosis: A Mechanistic and Pharmacological Review.Frontiers in cell and developmental biology · 2020Review
- DSPLMF: A Method for Cancer Drug Sensitivity Prediction Using a Novel Regularization Approach in Logistic Matrix Factorization.Frontiers in genetics · 2020Article
- The therapeutic properties of resminostat for hepatocellular carcinoma.Oncoscience · 2018Article
- Effects of DLC1 Deficiency on Endothelial Cell Contact Growth Inhibition and Angiosarcoma Progression.Journal of the National Cancer Institute · 2018Article
- Sub-cellular localization specific SUMOylation in the heart.Biochimica et biophysica acta. Molecular basis of disease · 2017Review
- Endotoxin- and mechanical stress-induced epigenetic changes in the regulation of the nicotinamide phosphoribosyltransferase promoter.Pulmonary circulation · 2016Article
- Disturbed Flow-Induced Endothelial Proatherogenic Signaling Via Regulating Post-Translational Modifications and Epigenetic Events.Antioxidants & redox signaling · 2016Review
- Identification of RNA-binding Proteins in Macrophages by Interactome Capture.Molecular & cellular proteomics : MCP · 2016Article
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Authors and funding
10 authors at 3 institutions in 1 country.
Funding
Abstract
Heat shock protein (hsp) 90 inhibition attenuates NF-κB activation and blocks inflammation. However, the precise mechanism of NF-κB regulation by hsp90 in the endothelium is not clear. We investigated the mechanisms of hsp90 inhibition by 17-N-allylamino-17-demethoxygeldanamycin (17-AAG) on NF-κB activation by LPS in primary human lung microvascular endothelial cells. Transcriptional activation of NF-κB was measured by luciferase reporter assay, gene expression by real-time RT-PCR, DNA binding of transcription factors by chromatin immunoprecipitation assay, protein-protein interaction by coimmunoprecipitation/immunoblotting, histone deacetylase (HDAC)/histone acetyltransferase enzyme activity by fluorometry, and nucleosome eviction by partial microccocal DNase digestion. In human lung microvascular endothelial cells, 17-AAG-induced degradation of IKBα was accomplished regardless of the phosphorylation/ubiquitination state of the protein. Hence, 17-AAG did not block LPS-induced NF-κB nuclear translocation and DNA binding activity. Instead, 17-AAG blocked the recruitment of the coactivator, cAMP response element binding protein binding protein, and prevented the assembly of a transcriptionally competent RNA polymerase II complex at the κB elements of the IKBα (an NF-κB-responsive gene) promoter. The effect of LPS on IKBα mRNA expression was associated with rapid deacetylation of histone-H3(Lys9) and a dramatic down-regulation of core histone H3 binding. Even though treatment with an HDAC inhibitor produced the same effect as hsp90 inhibition, the effect of 17-AAG was independent of HDAC. We conclude that hsp90 inhibition attenuates NF-κB transcriptional activation by preventing coactivator recruitment and nucleosome eviction from the target promoter in human lung endothelial cells.
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