ArticleThe Journal of biological chemistry2016
Differential Roles of Protein Complexes NOX1-NOXO1 and NOX2-p47phox in Mediating Endothelial Redox Responses to Oscillatory and Unidirectional Laminar Shear Stress.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 40 citations in OpenAlex.
- Proteomic Profiling of Endothelial Cells Under Laminar Shear Stress Confirms the Importance of KLF4 in the Regulation of Membrane Protein Expression Compared to Oscillatory Flow.Journal of proteome research · 2026Article
- Effects of the glucagon-like peptide-1 receptor agonist liraglutide on retinal endothelial function and oxidative stress during sepsis.Frontiers in pharmacology · 2026Article
- Interplay between energy metabolism and NADPH oxidase-mediated pathophysiology in cardiovascular diseases.Frontiers in pharmacology · 2024Review
- Characterizing nuclear morphology and expression of eNOS in vascular endothelial cells subjected to a continuous range of wall shear stress magnitudes and directionality.Journal of the mechanical behavior of biomedical materials · 2023Article
- Amelioration of endothelial dysfunction by sodium glucose co-transporter 2 inhibitors: pieces of the puzzle explaining their cardiovascular protection.British journal of pharmacology · 2022Review
- Flavored and Nicotine-Containing E-Cigarettes Induce Impaired Angiogenesis and Diabetic Wound Healing via Increased Endothelial Oxidative Stress and Reduced NO Bioavailability.Antioxidants (Basel, Switzerland) · 2022Article
- Disturbed flow's impact on cellular changes indicative of vascular aneurysm initiation, expansion, and rupture: A pathological and methodological review.Journal of cellular physiology · 2022Review
- Article
- MiR-155 acts as an inhibitory factor in atherosclerosis-associated arterial pathogenesis by down-regulating NoxA1 related signaling pathway in ApoECardiovascular diagnosis and therapy · 2021Article
- Biomechanical Forces and Oxidative Stress: Implications for Pulmonary Vascular Disease.Antioxidants & redox signaling · 2019Review
- The Role of NADPH Oxidases in the Etiology of Obesity and Metabolic Syndrome: Contribution of Individual Isoforms and Cell Biology.Antioxidants & redox signaling · 2019Review
- Oscillatory Shear Stress Induces Oxidative Stress via TLR4 Activation in Endothelial Cells.Mediators of inflammation · 2019Article
- The NADPH organizers NoxO1 and p47phox are both mediators of diabetes-induced vascular dysfunction in mice.Redox biology · 2018Article
- Endothelial Cell Metabolism.Physiological reviews · 2018Review
- Endothelium as a Potential Target for Treatment of Abdominal Aortic Aneurysm.Oxidative medicine and cellular longevity · 2018Review
- Mitochondrial CaJournal of the Royal Society, Interface · 2017Review
- Nox, Reactive Oxygen Species and Regulation of Vascular Cell Fate.Antioxidants (Basel, Switzerland) · 2017Review
- Peptide-Functionalized Fluorescent Particles for In Situ Detection of Nitric Oxide via Peroxynitrite-Mediated Nitration.Advanced healthcare materials · 2017Article
- Microvascular NADPH oxidase in health and disease.Free radical biology & medicine · 2017Review
- NADPH Oxidases, Angiogenesis, and Peripheral Artery Disease.Antioxidants (Basel, Switzerland) · 2017Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
The endothelium is exposed to various flow patterns such as vasoprotective unidirectional laminar shear stress (LSS) and atherogenic oscillatory shear stress (OSS). A software-controlled, valve-operated OsciFlow device with parallel chambers was used to apply LSS and OSS to endothelial cells. Although LSS inhibited superoxide over time, OSS time-dependently increased superoxide production from endothelial cells. Immunocytochemical staining revealed that, at resting state, p47phox colocalizes with NOX2, whereas NOXO1 colocalizes with NOX1. RNAi of p47phox had no effects on superoxide or NO production in response to OSS but significantly reduced NO production in LSS, implicating a p47phox-bound NADPH oxidase (NOX) in mediating basal NO production. Indeed, RNAi of p47phox inhibited endothelial nitric oxide synthase (eNOS) serine 1179 phosphorylation, whereas PEG-catalase scavenging of intracellular hydrogen peroxide or RNAi of NOX2 produced similar results, indicating a role of NOX2/p47phox-derived hydrogen peroxide in mediating the basal activity of NO production from eNOS. In contrast, RNAi of NOXO1 resulted in no significant changes in NO and superoxide levels in response to LSS but significantly reduced superoxide while increasing NO in response to OSS. Furthermore, we identified, for the first time, that OSS uncouples eNOS, which was corrected by RNAi of NOXO1. In summary, LSS activates the NOX2-p47phox complex to activate eNOS phosphorylation and NO production. OSS instead activates the NOX1-NOXO1 complex to uncouple eNOS. These results demonstrate differential roles of NOXs in modulating the redox state in response to different shear stresses, which may promote the development of novel therapeutic agents to mimic the protective effects of LSS while inhibiting the injurious effects of OSS.
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