ArticleMolecular and cellular biology2009
The hypoxia-inducible factor 1/NOR-1 axis regulates the survival response of endothelial cells to hypoxia.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 69 citations in OpenAlex.
- NOR-1 as a Context-Dependent Rheostat of Vascular and Cardiac Remodeling.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Review
- A mechanistic computational model of HGF-VEGF-mediated endothelial cell proliferation and vascular permeability.iScience · 2025Article
- Oxygen-Glucose Deprivation Increases NR4A1 Expression and Promotes Its Extranuclear Translocation in Mouse Astrocytes.Brain sciences · 2024Article
- Culture of Cancer Cells at Physiological Oxygen Levels Affects Gene Expression in a Cell-Type Specific Manner.Biomolecules · 2022Article
- Comprehensive insights into the function and molecular and pharmacological regulation of neuron-derived orphan receptor 1, an orphan receptor.Frontiers in pharmacology · 2022Review
- NR4A3: A Key Nuclear Receptor in Vascular Biology, Cardiovascular Remodeling, and Beyond.International journal of molecular sciences · 2021Review
- Irisin Protects the Human Placenta from Oxidative Stress and Apoptosis via Activation of the Akt Signaling Pathway.International journal of molecular sciences · 2021Article
- Overexpression of Neuron-Derived Orphan Receptor 1 (NOR-1) Rescues Cardiomyocytes from Cell Death and Improves Viability after Doxorubicin Induced Stress.Biomedicines · 2021Article
- Transcriptomic analysis of the mouse retina after acute and chronic normobaric and hypobaric hypoxia.Scientific reports · 2021Article
- SMARCB1 Promotes Ubiquitination and Degradation of NR4A3 via Direct Interaction Driven by ROS in Vascular Endothelial Cell Injury.Oxidative medicine and cellular longevity · 2020Article
- Hypoxia-mediated mitochondria apoptosis inhibition induces temozolomide treatment resistance through miR-26a/Bad/Bax axis.Cell death & disease · 2018Article
- Effect of asiaticoside on endothelial cells in hypoxia‑induced pulmonary hypertension.Molecular medicine reports · 2018Article
- Article
- NOR-1/NR4A3 regulates the cellular inhibitor of apoptosis 2 (cIAP2) in vascular cells: role in the survival response to hypoxic stress.Scientific reports · 2016Article
- Transcriptome analysis of human cumulus cells reveals hypoxia as the main determinant of follicular senescence.Molecular human reproduction · 2016Article
- The nuclear receptor NOR-1 regulates the small muscle protein, X-linked (SMPX) and myotube differentiation.Scientific reports · 2016Article
- The interplay of NR4A receptors and the oncogene-tumor suppressor networks in cancer.Cellular signalling · 2015Review
- Rotenone induction of hydrogen peroxide inhibits mTOR-mediated S6K1 and 4E-BP1/eIF4E pathways, leading to neuronal apoptosis.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- miR-17 and -20a Target the Neuron-Derived Orphan Receptor-1 (NOR-1) in Vascular Endothelial Cells.PloS one · 2015Article
- Peripheral arterial disease, type 2 diabetes and postprandial lipidaemia: Is there a link?World journal of diabetes · 2014Review
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia induces apoptosis but also triggers adaptive mechanisms to ensure cell survival. Here we show that the prosurvival effects of hypoxia-inducible factor 1 (HIF-1) in endothelial cells are mediated by neuron-derived orphan receptor 1 (NOR-1). The overexpression of NOR-1 decreased the rate of endothelial cells undergoing apoptosis in cultures exposed to hypoxia, while the inhibition of NOR-1 increased cell apoptosis. Hypoxia upregulated NOR-1 mRNA levels in a time- and dose-dependent manner. Blocking antibodies against VEGF or SU5614 (a VEGF receptor 2 inhibitor) did not prevent hypoxia-induced NOR-1 expression, suggesting that NOR-1 is not induced by the autocrine secretion of VEGF in response to hypoxia. The reduction of HIF-1 alpha protein levels by small interfering RNAs, or by inhibitors of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway or mTOR, significantly counteracted hypoxia-induced NOR-1 upregulation. Intracellular Ca(2+) was involved in hypoxia-induced PI3K/Akt activation and in the downstream NOR-1 upregulation. A hypoxia response element mediated the transcriptional activation of NOR-1 induced by hypoxia as we show by transient transfection and chromatin immunoprecipitation assays. Finally, the attenuation of NOR-1 expression reduced both basal and hypoxia-induced cIAP2 (cellular inhibitor of apoptosis protein 2) mRNA levels, while NOR-1 overexpression upregulated cIAP2. Therefore, NOR-1 is a downstream effector of HIF-1 signaling involved in the survival response of endothelial cells to hypoxia.
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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.