ArticleHypertension (Dallas, Tex. : 1979)2015
Activation of nuclear factor erythroid 2-related factor 2 coordinates dimethylarginine dimethylaminohydrolase/PPAR-γ/endothelial nitric oxide synthase pathways that enhance nitric oxide generation in human glomerular endothelial cells.
Article in Hypertension (Dallas, Tex. : 1979), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 1 of them a synthesis that pooled it.
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Who cites it
26 citing papers in PubMed, 1 synthesis or guideline pooled it, 42 citations in OpenAlex.
- Oxidative Stress and Cardiovascular Aging: Interaction Between NRF-2 and ADMA.Current cardiology reviews · 2017Pooled it
- Nephrotoxicity of Evodiamine in Mice: Mechanistic Insights from Integrated Network Toxicology and Transcriptomic Profiling.International journal of molecular sciences · 2026Article
- Superoxide signals for the mitophagy of dysfunctional mitochondria to maintain quality control.Redox biology · 2026Review
- Redox Regulation of Endogenous Gasotransmitters in Vascular Health and Disease.International journal of molecular sciences · 2025Review
- Nrf2-Keap1 in Cardiovascular Disease: Which Is the Cart and Which the Horse?Physiology (Bethesda, Md.) · 2024Review
- SARS-CoV-2 infection and dysregulation of nuclear factor erythroid-2-related factor 2 (Nrf2) pathway.Cell stress & chaperones · 2023Review
- PPARγ in Atherosclerotic Endothelial Dysfunction: Regulatory Compounds and PTMs.International journal of molecular sciences · 2023Review
- Insights into the Molecular Mechanisms of NRF2 in Kidney Injury and Diseases.International journal of molecular sciences · 2023Review
- Activation of the Nrf-2/HO-1 signalling axis can alleviate metabolic syndrome in cardiovascular disease.Annals of medicine · 2023Review
- N-acetylcysteine improves diabetic associated erectile dysfunction in streptozotocin-induced diabetic mice by inhibiting oxidative stress.Journal of cellular and molecular medicine · 2022Article
- Activation of Nrf2 in Mice Causes Early Microvascular Cyclooxygenase-Dependent Oxidative Stress and Enhanced Contractility.Antioxidants (Basel, Switzerland) · 2022Article
- Endothelial Cullin3 Mutation Impairs Nitric Oxide-Mediated Vasodilation and Promotes Salt-Induced Hypertension.Function (Oxford, England) · 2022Article
- Role of the Peroxisome Proliferator Activated Receptors in Hypertension.Circulation research · 2021Review
- Nrf2 inhibition induces oxidative stress, renal inflammation and hypertension in mice.Clinical and experimental hypertension (New York, N.Y. : 1993) · 2021Article
- Cullin-3: Renal and Vascular Mechanisms Regulating Blood Pressure.Current hypertension reports · 2020Review
- (-)-Epicatechin Reduces the Blood Pressure of Young Borderline Hypertensive Rats During the Post-Treatment Period.Antioxidants (Basel, Switzerland) · 2020Article
- Protective Effects of Caffeic Acid Phenethyl Ester (CAPE) and Novel Cape Analogue as Inducers of Heme Oxygenase-1 in Streptozotocin-Induced Type 1 Diabetic Rats.International journal of molecular sciences · 2019Article
- Inhibition of Dimethylarginine Dimethylaminohydrolase (DDAH) Enzymes as an Emerging Therapeutic Strategy to Target Angiogenesis and Vasculogenic Mimicry in Cancer.Frontiers in oncology · 2019Review
- NRF2 prevents hypertension, increased ADMA, microvascular oxidative stress, and dysfunction in mice with two weeks of ANG II infusion.American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Haematoma scavenging in intracerebral haemorrhage: from mechanisms to the clinic.Journal of cellular and molecular medicine · 2018Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Dimethylarginine dimethylaminohydrolase (DDAH) degrades asymmetric dimethylarginine, which inhibits nitric oxide (NO) synthase (NOS). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcriptional factor that binds to antioxidant response elements and transcribes many antioxidant genes. Because the promoters of the human DDAH-1 and DDAH-2, endothelial NOS (eNOS) and PPAR-γ genes contain 2 to 3 putative antioxidant response elements, we hypothesized that they were regulated by Nrf2/antioxidant response element. Incubation of human renal glomerular endothelial cells with the Nrf2 activator tert-butylhydroquinone (20 μmol·L(-1)) significantly (P<0.05) increased NO and activities of NOS and DDAH and decreased asymmetric dimethylarginine. It upregulated genes for hemoxygenase-1, eNOS, DDAH-1, DDAH-2, and PPAR-γ and partitioned Nrf2 into the nucleus. Knockdown of Nrf2 abolished these effects. Nrf2 bound to one antioxidant response element on DDAH-1 and DDAH-2 and PPAR-γ promoters but not to the eNOS promoter. An increased eNOS and phosphorylated eNOS (P-eNOSser-1177) expression with tert-butylhydroquinone was prevented by knockdown of PPAR-γ. Expression of Nrf2 was reduced by knockdown of PPAR-γ, whereas PPAR-γ was reduced by knockdown of Nrf2, thereby demonstrating 2-way positive interactions. Thus, Nrf2 transcribes HO-1 and other genes to reduce reactive oxygen species, and DDAH-1 and DDAH-2 to reduce asymmetric dimethylarginine and PPAR-γ to increase eNOS and its phosphorylation and activity thereby coordinating 3 pathways that enhance endothelial NO generation.
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Registered trials
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