ArticleEndocrinology2008
Endothelin (ET)-1 inhibits nicotinamide adenine dinucleotide phosphate oxidase activity in human abdominal aortic endothelial cells: a novel function of ETB1 receptors.
Article in Endocrinology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 25 citations in OpenAlex.
- TNFα Induces DNA and Histone Hypomethylation and Pulmonary Artery Smooth Muscle Cell Proliferation Partly via Excessive Superoxide Formation.Antioxidants (Basel, Switzerland) · 2024Article
- Endothelium-restricted endothelin-1 overexpression in type 1 diabetes worsens atherosclerosis and immune cell infiltration via NOX1.Cardiovascular research · 2021Article
- Beneficial Effect of Bariatric Surgery on Abnormal MMP-9 and AMPK Activities: Potential Markers of Obesity-Related CV Risk.Frontiers in physiology · 2019Article
- Activation of SIRT1 Attenuates Klotho Deficiency-Induced Arterial Stiffness and Hypertension by Enhancing AMP-Activated Protein Kinase Activity.Hypertension (Dallas, Tex. : 1979) · 2016Article
- Endothelin Receptors Expressed by Immune Cells Are Involved in Modulation of Inflammation and in Fibrosis: Relevance to the Pathogenesis of Systemic Sclerosis.Journal of immunology research · 2015Article
- Normal IgG downregulates the intracellular superoxide level and attenuates migration and permeability in human aortic endothelial cells isolated from a hypertensive patient.Hypertension (Dallas, Tex. : 1979) · 2012Article
- Klotho gene delivery suppresses Nox2 expression and attenuates oxidative stress in rat aortic smooth muscle cells via the cAMP-PKA pathway.Aging cell · 2012Article
- Biochemistry, physiology, and pathophysiology of NADPH oxidases in the cardiovascular system.Circulation research · 2012Review
- Genetic interleukin-10 deficiency causes vascular remodeling via the upregulation of Nox1.Journal of hypertension · 2011Article
- Aging-related kidney damage is associated with a decrease in klotho expression and an increase in superoxide production.Age (Dordrecht, Netherlands) · 2011Article
- Relationship between stem cell factor/c-kit expression in peripheral blood and blood pressure.Journal of human hypertension · 2010Article
- Klotho gene delivery prevents the progression of spontaneous hypertension and renal damage.Hypertension (Dallas, Tex. : 1979) · 2009Article
- Vascular Smooth Muscle Cell Signaling Mechanisms for Contraction to Angiotensin II and Endothelin-1.Journal of the American Society of Hypertension : JASHArticle
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Endothelin (ET)-1 stimulates nicotinamide adenine dinucleotide phosphate (NADPH) oxidases and increases superoxide production in some cells such as vascular smooth muscle cells. Here, we reported that ET1 inhibited NADPH oxidase activity, superoxide generation, and cell proliferation in human abdominal aortic endothelial cells (HAAECs) via the ETB1-Pyk2-Rac1-Nox1 pathway. Superoxide production was determined by assessing ethidium fluorescence using flow cytometry in HAAECs exposed to ET1 (10-30 nm) at different time intervals. ET1 significantly decreased superoxide production in HAAECs in the presence of NG-nitro-L-arginine methyl ester, indicating that ET1 suppressed superoxide generation independent of nitric oxide synthase. ET1 significantly attenuated NADPH oxidase activity and cell proliferation, which could be abolished by silence of Nox1 gene, suggesting that ET1-induced inhibition of NADPH oxidase activity was mediated by Nox1. Furthermore, RNA interference silence of ETB1 receptors significantly increased NADPH oxidase activity, and blocked the inhibitory effect of ET1 on NADPH oxidase activity. Activation of ETB1 receptors by ET1 suppressed protein phosphorylation of pyk2 (Y402) and Rac1, suggesting that ET1 inhibited NADPH oxidase activity via ETB1-Pyk2-Rac1 pathway. Indeed, inhibition of Pyk2 by AG-17 abolished ET1-induced suppression of NADPH oxidase activity. ET1 also attenuated angiotensin II-induced activation of NADPH oxidase and cell proliferation. This study demonstrated, for the first time, that ET1, via ETB1, inhibited NADPH oxidase activity in HAAECs by suppressing the Pyk2-Rac1-Nox1 pathway. This finding reveals a novel function of ETB1 receptors in regulating endothelial NADPH oxidase activity, superoxide production, and cell proliferation, opening a new avenue for understanding the role of ETB1 receptors in protecting endothelial cells.
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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.