ArticleThe Journal of biological chemistry2013
Endothelial nitric-oxide synthase activation generates an inducible nitric-oxide synthase-like output of nitric oxide in inflamed endothelium.
Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers.
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Who cites it
38 citing papers in PubMed, 58 citations in OpenAlex.
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- An integrative single-nucleus multiomic atlas of the human left ventricle identifies gene regulatory network dynamics across cardiac development, aging, and disease.Genome biology · 2026Article
- Integrating endothelium-derived hyperpolarization, nitric oxide, and prostacyclin pathways: the multimodal potential of human tissue kallikrein-1.Vascular biology (Bristol, England) · 2025Review
- The vascular endothelium as decision maker in lung injury.Frontiers in cell and developmental biology · 2025Review
- Article
- The Role of Inducible Nitric Oxide Synthase in Assessing the Functional Level of Coronary Artery Lesions in Chronic Coronary Syndrome.Cardiology research · 2024Review
- Optimizing irradiation conditions for low-intensity pulsed ultrasound to upregulate endothelial nitric oxide synthase.Journal of medical ultrasonics (2001) · 2024Article
- Growth hormone - releasing hormone in the context of inflammation and redox biology.Frontiers in immunology · 2024Article
- Minimal Change Disease Is Associated With Endothelial Glycocalyx Degradation and Endothelial Activation.Kidney international reports · 2022Article
- Modulating the Antioxidant Response for Better Oxidative Stress-Inducing Therapies: How to Take Advantage of Two Sides of the Same Medal?Biomedicines · 2022Review
- A human pluripotent stem cell-based model of SARS-CoV-2 infection reveals an ACE2-independent inflammatory activation of vascular endothelial cells through TLR4.Stem cell reports · 2022Article
- JEV Infection Induces M-MDSC Differentiation Into CD3Frontiers in immunology · 2022Article
- Role of Vascular Smooth Muscle Cell Phenotype Switching in Arteriogenesis.International journal of molecular sciences · 2021Review
- Multifaced Roles of HDL in Sepsis and SARS-CoV-2 Infection: Renal Implications.International journal of molecular sciences · 2021Review
- Type 2 diabetes progression differently affects endothelial function and vascular contractility in the aorta and the pulmonary artery.Scientific reports · 2021Article
- UPLC-ESI-Q-TOF-MS-Based Metabolite Profiling, Antioxidant and Anti-Inflammatory Properties of Different Organ Extracts ofAntioxidants (Basel, Switzerland) · 2021Article
- Schisandrin B Attenuates Airway Inflammation by Regulating the NF-Journal of immunology research · 2021Article
- Mineralocorticoid Receptor in Myeloid Cells Mediates Angiotensin II-Induced Vascular Dysfunction in Female Mice.Frontiers in physiology · 2021Article
- Does eNOS derived nitric oxide protect the young from severe COVID-19 complications?Ageing research reviews · 2020Review
- Role of Endothelial G Protein-Coupled Receptor Kinase 2 in Angioedema.Hypertension (Dallas, Tex. : 1979) · 2020Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
High levels of NO generated in the vasculature under inflammatory conditions are usually attributed to inducible nitric-oxide synthase (iNOS), but the role of the constitutively expressed endothelial NOS (eNOS) is unclear. In normal human lung microvascular endothelial cells (HLMVEC), bradykinin (BK) activates kinin B2 receptor (B2R) signaling that results in Ca(2+)-dependent activation of eNOS and transient NO. In inflamed HLMVEC (pretreated with interleukin-1β and interferon-γ), we found enhanced binding of eNOS to calcium-calmodulin at basal Ca(2+) levels, thereby increasing its basal activity that was dependent on extracellular l-Arg. Furthermore, B2R stimulation generated prolonged high output eNOS-derived NO that is independent of increased intracellular Ca(2+) and is mediated by a novel Gα(i)-, MEK1/2-, and JNK1/2-dependent pathway. This high output NO stimulated with BK was blocked with a B2R antagonist, eNOS siRNA, or eNOS inhibitor but not iNOS inhibitor. Moreover, B2R-mediated NO production and JNK phosphorylation were inhibited with MEK1/2 and JNK inhibitors or MEK1/2 and JNK1/2 siRNA but not with ERK1/2 inhibitor. BK induced Ca(2+)-dependent eNOS phosphorylation at Ser(1177), Thr(495), and Ser(114) in cytokine-treated HLMVEC, but these modifications were not dependent on JNK1/2 activation and were not responsible for prolonged NO output. Cytokine treatment did not alter the expression of B2R, Gα(q/11), Gα(i1,2), JNK, or eNOS. B2R activation in control endothelial cells enhanced migration, but in cytokine-treated HLMVEC it reduced migration. Both responses were NO-dependent. Understanding how JNK regulates prolonged eNOS-derived NO may provide new therapeutic targets for the treatment of disorders involving vascular inflammation.
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