ArticleDiabetologia2012
The p47phox- and NADPH oxidase organiser 1 (NOXO1)-dependent activation of NADPH oxidase 1 (NOX1) mediates endothelial nitric oxide synthase (eNOS) uncoupling and endothelial dysfunction in a streptozotocin-induced murine model of diabetes.
Article in Diabetologia, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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Who cites it
81 citing papers in PubMed, 125 citations in OpenAlex.
- Endothelial NOX1 Drives Obesity via Skeletal Muscle Mitochondrial Dysfunction.Circulation research · 2026Article
- eNOS Uncoupling-ER Stress-Mitochondrial Dysfunction Axis in the Development of Pulmonary Hypertension.JACC. Basic to translational science · 2026Article
- Oxidative Stress in Diabetic Cardiomyopathy: Molecular Mechanisms and Emerging Therapeutic Targets.Biomolecules · 2026Review
- Folic Acid Therapy is Associated with a Lower Risk of Incident Diabetes and Better Glycemic Status in Patients with Coronary Heart Disease: Findings from a Multicenter Propensity Score-Matched Analysis.Drug design, development and therapy · 2026Article
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Interdisciplinary perspectives on diabetes and microcirculatory dysfunction: A global bibliometric analysis.World journal of diabetes · 2025Article
- Delineating the NOX-Mediated Promising Therapeutic Strategies for the Management of Various Cardiovascular Disorders: A Comprehensive Review.Current vascular pharmacology · 2025Review
- NADPH Oxidase 5 (NOX5) Upregulates MMP-10 Production and Cell Migration in Human Endothelial Cells.Antioxidants (Basel, Switzerland) · 2024Article
- The effects of ecdysterone and enalapril on nitric oxide synthesis and the markers of oxidative stress in streptozotocin-induced diabetes in rats: a comparative study.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.Molecules (Basel, Switzerland) · 2024Review
- Reversal of Pulmonary Hypertension in a Human-Like Model: Therapeutic Targeting of Endothelial DHFR.Circulation research · 2024Article
- Type 1 Diabetes Impairs Endothelium-Dependent Relaxation Via Increasing Endothelial Cell Glycolysis Through Advanced Glycation End Products, PFKFB3, and Nox1-Mediated Mechanisms.Hypertension (Dallas, Tex. : 1979) · 2023Article
- Exercise and vascular function in sedentary lifestyles in humans.Pflugers Archiv : European journal of physiology · 2023Review
- Increased NOX2 expression in astrocytes leads to eNOS uncoupling through dihydrofolate reductase in endothelial cells after subarachnoid hemorrhage.Frontiers in molecular neuroscience · 2023Article
- Oxidative Regulation of Vascular CaAntioxidants (Basel, Switzerland) · 2022Review
- NOX1 mediates metabolic heart disease in mice and is upregulated in monocytes of humans with diastolic dysfunction.Cardiovascular research · 2022Article
- The NADPH oxidase NOX2 is a marker of adverse prognosis involved in chemoresistance of acute myeloid leukemias.Haematologica · 2022Article
- Diagnostic and predictive values of circulating tetrahydrobiopterin levels as a novel biomarker in patients with thoracic and abdominal aortic aneurysms.Redox biology · 2022Article
- NADPH Oxidase Isoforms in COPD Patients and Acute Cigarette Smoke-Exposed Mice: Induction of Oxidative Stress and Lung Inflammation.Antioxidants (Basel, Switzerland) · 2022Article
- Hyperoxaluria Induces Endothelial Dysfunction in Preglomerular Arteries: Involvement of Oxidative Stress.Cells · 2022Article
21 more citing papers are in PubMed but not listed here.
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3 authors at 1 institution in 1 country.
Funding
Abstract
aims/hypothesisWe have previously shown that NADPH oxidase (NOX) lies upstream of uncoupled endothelial nitric oxide synthase (eNOS), which is known to occur in diabetic endothelium. However, it remains unclear which specific NOX isoform(s) is responsible for eNOS uncoupling and endothelial dysfunction in diabetic mouse models. The aim of the present study was to test the hypothesis that one or more NOX isoform(s) mediate(s) diabetic uncoupling of eNOS, which has been shown to occur in patients with diabetes to contribute to endothelial dysfunction.
methodsDiabetes was induced by streptozotocin administration. The N (ω)-nitro-L-arginine methyl ester (L-NAME)-sensitive superoxide production of aortic segments, reflective of eNOS uncoupling activity, was determined by electron spin resonance.
resultsThe L-NAME-sensitive superoxide production was more than doubled in wild-type diabetic mice, implicating uncoupling of eNOS. This was abolished in diabetic p47 ( phox-/-) (also known as Ncf1 (-/-)) mice, but preserved in Nox2 (-/y) (also known as Cybb (-/-)) mice made diabetic. The eNOS uncoupling activity was markedly attenuated in diabetic mice transfected with Nox1 or Nox1 organiser 1 (Noxo1) short interfering RNA (siRNA), and abolished in Nox1 (-/y) diabetic mice. Diabetes-induced impairment in endothelium-dependent vasorelaxation was also significantly attenuated in the Nox1 (-/y) mice made diabetic. By contrast, Nox4 siRNA, or inhibition of mitochondrial complex I or III with rotenone or siRNA, respectively, had no effect on diabetic uncoupling of eNOS. Overexpression of Dhfr, or oral administration of folic acid to improve dihydrofolate reductase (DHFR) function, recoupled eNOS in diabetes to improve endothelial function. CONCLUSIONS/
interpretationOur data demonstrate for the first time that the p47(phox) and NOXO1-dependent activation of NOX1, but not that of NOX2, NOX4 or mitochondrion, mediates diabetic uncoupling of eNOS. NOX1-null mice are protected from diabetic endothelial dysfunction. Novel approaches to inhibit NOX1 and/or improve DHFR function, may prove to have therapeutic potential for diabetic endothelial dysfunction.
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