ArticleThe Journal of biological chemistry2009
Active NF-E2-related factor (Nrf2) contributes to keep endothelial NO synthase (eNOS) in the coupled state: role of reactive oxygen species (ROS), eNOS, and heme oxygenase (HO-1) levels.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 87 citations in OpenAlex.
- Estrogen receptor and PI3K/Akt signaling pathway involvement in S-(-)equol-induced activation of Nrf2/ARE in endothelial cells.PloS one · 2013Trial
- Understanding physiological adaptations of pregnancy to the chronic hypoxia of high altitude to inform obstetrical and neonatal care.Physiological reviews · 2026Review
- Effects of Environmental Temperature During Cultivation of Broccoli Microgreens on Hematological Parameters, Molecular Markers, and Myocardial Antioxidant Status in Swiss Mice.Food science & nutrition · 2026Article
- Inhibition of smooth muscle phenotypic modulation by bardoxolone methyl, omaveloxolone, and cinnamaldehyde is Nrf-2 dependent.Advances in redox research · 2026Article
- Superoxide signals for the mitophagy of dysfunctional mitochondria to maintain quality control.Redox biology · 2026Review
- Emerging Biomarkers and Innovative Therapeutic Strategies in Diabetic Kidney Disease: A Pathway to Precision Medicine.Diagnostics (Basel, Switzerland) · 2025Review
- Edible mushroom (Anatomy & cell biology · 2024Article
- Insulin and aging - a disappointing relationship.Frontiers in endocrinology · 2023Review
- Role of curcumin in ameliorating hypertension and associated conditions: a mechanistic insight.Molecular and cellular biochemistry · 2022Review
- Metabolic Changes and Oxidative Stress in Diabetic Kidney Disease.Antioxidants (Basel, Switzerland) · 2021Review
- Treatment of Diabetic Kidney Disease: Current and Future.Diabetes & metabolism journal · 2021Review
- Pharmacological Activation of Nrf2 by Rosolic Acid Attenuates Endoplasmic Reticulum Stress in Endothelial Cells.Oxidative medicine and cellular longevity · 2021Article
- Targeting Transcription Factor Nrf2 (Nuclear Factor Erythroid 2-Related Factor 2) for the Intervention of Vascular Cognitive Impairment and Dementia.Arteriosclerosis, thrombosis, and vascular biology · 2021Review
- Bardoxolone methyl: drug development for diabetic kidney disease.Clinical and experimental nephrology · 2020Review
- Interaction Between NOS3 and HMOX1 on Antihypertensive Drug Responsiveness in Preeclampsia.Revista brasileira de ginecologia e obstetricia : revista da Federacao Brasileira das Sociedades de Ginecologia e Obstetricia · 2020Article
- Flavonoids Activation of the Transcription Factor Nrf2 as a Hypothesis Approach for the Prevention and Modulation of SARS-CoV-2 Infection Severity.Antioxidants (Basel, Switzerland) · 2020Article
- Randomized Clinical Trial on the Effect of Bardoxolone Methyl on GFR in Diabetic Kidney Disease Patients (TSUBAKI Study).Kidney international reports · 2020Article
- Pulmonary Arterial Hypertension and Chronic Thromboembolic Pulmonary Hypertension: An Immunological Perspective.Journal of clinical medicine · 2020Review
- Association of single nucleotide polymorphisms in the NRF2 promoter with vascular stiffness with aging.PloS one · 2020Article
- Zingerone attenuates aortic banding-induced cardiac remodelling via activating the eNOS/Nrf2 pathway.Journal of cellular and molecular medicine · 2019Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The aim of our study was to examine in detail the impact of NF-E2-related factor (Nrf2) activation on endothelial cell function with focus on redox homeostasis and the endothelial nitric oxide synthase (eNOS) system. We administered 2-cyano-3,12-dioxooleana-1,9-dien-28-oic imidazolide (CDDO-IM), a known activator of Nrf2, to primary human umbilical vein endothelial cells. Activation of Nrf2 by CDDO-IM increased the amount of bioavailable nitric oxide (NO), a major contributor to vascular homeostasis, in naive and stressed cells. Concomitantly, intracellular reactive oxygen species were dose-and time-dependently reduced. In apparent contrast to elevated NO levels, eNOS protein expression was transiently decreased in an Nrf2-dependent manner. Employing pharmacological inhibitors as well as a small interfering RNA approach, we identified de novo protein synthesis of heme oxygenase 1 (HO-1) and its enzymatic activity as cause for the observed reduction of eNOS. We hypothesize that under redox stress, when the availability of tetrahydrobiopterin, a pivotal stoichiometric cofactor for eNOS, is limited, activation of Nrf2 leads (a) to transient reduction of eNOS protein levels and (b) to an antioxidant defense in human umbilical vein endothelial cells. Both activities ensure that a stoichiometric ratio of eNOS and tetrahydrobiopterin is sustained and that the risk of eNOS uncoupling is reduced. Our study is the first to provide a causal link between Nrf2 activation and eNOS expression and NO levels, respectively.
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