ArticleCardiovascular pharmacology: open access2015
A Novel ASK Inhibitor AGI-1067 Inhibits TLR-4-Mediated Activation of ASK1 by Preventing Dissociation of Thioredoxin from ASK1.
Article in Cardiovascular pharmacology: open access, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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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.
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Who cites it
3 citing papers in PubMed, 10 citations in OpenAlex.
- Ox-LDL Causes Endothelial Cell Injury Through ASK1/NLRP3-Mediated Inflammasome Activation via Endoplasmic Reticulum Stress.Drug design, development and therapy · 2020Article
- Novel ASK1 inhibitor AGI-1067 improves AGE-induced cardiac dysfunction by inhibiting MKKs/p38 MAPK and NF-κB apoptotic signaling.FEBS open bio · 2018Article
- Cell Type-Specific Mechanisms in the Pathogenesis of Ischemic Stroke: The Role of Apoptosis Signal-Regulating Kinase 1.Oxidative medicine and cellular longevity · 2018Review
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
The cell type that normally limits the inflammatory and atherosclerotic process is the vascular endothelial cell (EC) that can be regulated by proinflammatory and various stresses. Toll-like receptor-4 (TLR4) plays an important role in the pathogenesis of atherosclerosis, in part, by activating apoptosis signal-regulating kinase 1 (ASK1) to initiate the activation of MAP kinases pathways and the expression of inflammatory genes. In the present study, we test the hypothesis that AGI-1067 acts as an anti-inflammatory agent by inhibiting the activation of ASK1 in human EC. Pretreatment of human aortic endothelial cells with AGI-1067 inhibits TLR4 ligand (LPS)-induced activation of ASK1 and the downstream p38 and c-Jun N-terminal kinase (JNK) MAP kinases. LPS dissociates two endogenous inhibitors thioredoxin-1 (Trx1) and 14-3-3 from ASK1, leading to ASK1 autoactivation. Interestingly, AGI-1067 inhibits the dissociation of Trx1, but not 14-3-3, from ASK1. However, inhibition of Trx1 dissociation from ASK1 by AGI-1067 is sufficient to suppress LPS-mediated phosphorylation of the transcription factors c-Jun and activating transcription factor 2, and inhibit LPS-induced inflammatory genes including vascular cell adhesion molecule 1, E-selectin, IL-6 and monocyte chemoattractant protein 1. Our findings suggest that AGI-1067 as a unique ASK1 inhibitor to inhibit TLR4-mediated ASK1 activation, contributing to its anti-inflammatory properties.
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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.