ArticleThe Journal of biological chemistry2014
Unspliced X-box-binding protein 1 (XBP1) protects endothelial cells from oxidative stress through interaction with histone deacetylase 3.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers, 1 of them a synthesis that pooled it.
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Who cites it
51 citing papers in PubMed, 1 synthesis or guideline pooled it, 94 citations in OpenAlex.
- Histone modification of endothelial-mesenchymal transition in cardiovascular diseases.Frontiers in cardiovascular medicine · 2022Pooled it
- Translating the Crosstalk Between Unfolded Protein Response and Ferroptosis to Cancer Therapies.Current oncology reports · 2026Review
- Qishen Yiqi Dripping Pills Activate HDAC3-Mediated Nrf2-PITX2 Signaling Pathway to Reduce Oxidative Stress and Alleviate Myocardial Infarction Injury in Mice.Chinese journal of integrative medicine · 2026Article
- HDAC3 activates endothelial NLRP3 inflammasome and promotes atherosclerosis via inhibiting the acetylation of specificity protein 1.Cell death and differentiation · 2026Article
- Harnessing lipid-driven immunometabolic pathways in omental metastases to enhance immunotherapy in patients with ovarian cancer.Signal transduction and targeted therapy · 2026Article
- Defining the role of β-cell IRE1α/XBP1 pathway and its gene regulatory network components in non-obese diabetic mice.Nature communications · 2025Article
- X26nt-mediated recruitment of eIF4A2 facilitates CCND1 translation to drive endothelial cell cycle progression.Genes & diseases · 2025Article
- Role of Endoplasmic Reticulum Stress-Associated Genes in Septic Neonatal Foals.Antioxidants (Basel, Switzerland) · 2025Article
- Mechanistic insights and emerging therapeutic strategies targeting endothelial dysfunction in cardiovascular diseases.Archives of pharmacal research · 2025Review
- Endothelial cells under disturbed flow release extracellular vesicles to promote inflammatory polarization of macrophages and accelerate atherosclerosis.BMC biology · 2025Article
- Roles of X-box binding protein 1 in liver pathogenesis.Clinical and molecular hepatology · 2025Review
- Developmental endothelial locus 1: the present and future of an endogenous factor in vessels.Frontiers in physiology · 2024Review
- XBP1 Modulates the Aging Cardiorenal System by Regulating Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- Identification of the role of endoplasmic reticulum stress genes in endometrial cancer and their association with tumor immunity.BMC medical genomics · 2023Article
- Immunomodulatory Effect of Proteasome Inhibitors via the Induction of Immunogenic Cell Death in Myeloma Cells.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Decrotonylation of AKT1 promotes AKT1 phosphorylation and activation during myogenic differentiation.Journal of advanced research · 2023Article
- Unfolding the Interactions between Endoplasmic Reticulum Stress and Oxidative Stress.Antioxidants (Basel, Switzerland) · 2023Review
- The role of HDAC3 and its inhibitors in regulation of oxidative stress and chronic diseases.Cell death discovery · 2023Review
- X-box Binding Protein 1: An Adaptor in the Pathogenesis of Atherosclerosis.Aging and disease · 2023Review
- Cathepsin K contributed to disturbed flow-induced atherosclerosis is dependent on integrin-actin cytoskeleton-NF-κB pathway.Genes & diseases · 2023Article
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
It is well known that atherosclerosis occurs geographically at branch points where disturbed flow predisposes to the development of plaque via triggering of oxidative stress and inflammatory reactions. In this study, we found that disturbed flow activated anti-oxidative reactions via up-regulating heme oxygenase 1 (HO-1) in an X-box-binding protein 1 (XBP1) and histone deacetylase 3 (HDAC3)-dependent manner. Disturbed flow concomitantly up-regulated the unspliced XBP1 (XBP1u) and HDAC3 in a VEGF receptor and PI3K/Akt-dependent manner. The presence of XBP1 was essential for the up-regulation of HDAC3 protein. Overexpression of XBP1u and/or HDAC3 activated Akt1 phosphorylation, Nrf2 protein stabilization and nuclear translocation, and HO-1 expression. Knockdown of XBP1u decreased the basal level and disturbed flow-induced Akt1 phosphorylation, Nrf2 stabilization, and HO-1 expression. Knockdown of HDAC3 ablated XBP1u-mediated effects. The mammalian target of rapamycin complex 2 (mTORC2) inhibitor, AZD2014, ablated XBP1u or HDAC3 or disturbed flow-mediated Akt1 phosphorylation, Nrf2 nuclear translocation, and HO-1 expression. Neither actinomycin D nor cycloheximide affected disturbed flow-induced up-regulation of Nrf2 protein. Knockdown of Nrf2 abolished XBP1u or HDAC3 or disturbed flow-induced HO-1 up-regulation. Co-immunoprecipitation assays demonstrated that XBP1u physically bound to HDAC3 and Akt1. The region of amino acids 201 to 323 of the HDAC3 protein was responsible for the binding to XBP1u. Double immunofluorescence staining revealed that the interactions between Akt1 and mTORC2, Akt1 and HDAC3, Akt1 and XBP1u, HDAC3, and XBP1u occurred in the cytosol. Thus, we demonstrate that XBP1u and HDAC3 exert a protective effect on disturbed flow-induced oxidative stress via up-regulation of mTORC2-dependent Akt1 phosphorylation and Nrf2-mediated HO-1 expression.
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