ArticleCirculation research2010
Upregulation of Nox4 by TGF{beta}1 oxidizes SERCA and inhibits NO in arterial smooth muscle of the prediabetic Zucker rat.
Article in Circulation research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 57 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
57 citing papers in PubMed, 111 citations in OpenAlex.
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- A Novel PPARγ Modulator Falcarindiol Mediates ER Stress-Mediated Apoptosis by Regulating NOX4 and Overcomes Radioresistance in Breast Cancer.Antioxidants (Basel, Switzerland) · 2024Article
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Nox4 as a novel therapeutic target for diabetic vascular complications.Redox biology · 2023Review
- Alterations of the CaFrontiers in physiology · 2023Article
- The substitution of SERCA2 redox cysteine 674 promotes pulmonary vascular remodeling by activating IRE1Acta pharmaceutica Sinica. B · 2022Article
- Peripheral vascular remodeling during ischemia.Frontiers in pharmacology · 2022Review
- Pathways Linking Nicotinamide Adenine Dinucleotide Phosphate Production to Endoplasmic Reticulum Protein Oxidation and Stress.Frontiers in molecular biosciences · 2022Review
- Reactive Oxygen Species and Endothelial CaInternational journal of molecular sciences · 2021Review
- Sestrin2 Attenuates Cellular Senescence by Inhibiting NADPH Oxidase 4 Expression.Annals of geriatric medicine and research · 2020Article
- Review
- Inactivation of CysBritish journal of pharmacology · 2020Article
- Integrated miRNA/mRNA Counter-Expression Analysis Highlights Oxidative Stress-Related GenesInternational journal of molecular sciences · 2020Article
- Type 2 Diabetes Alters Intracellular CaInternational journal of molecular sciences · 2019Article
- Cysteine Glutathionylation Acts as a Redox Switch in Endothelial Cells.Antioxidants (Basel, Switzerland) · 2019Review
- Vascular smooth muscle-MAPK14 is required for neointimal hyperplasia by suppressing VSMC differentiation and inducing proliferation and inflammation.Redox biology · 2019Article
- BIAM switch assay coupled to mass spectrometry identifies novel redox targets of NADPH oxidase 4.Redox biology · 2019Article
- Role of TG2-Mediated SERCA2 Serotonylation on Hypoxic Pulmonary Vein Remodeling.Frontiers in pharmacology · 2019Article
Corrections and comments
- Erratum issued
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
rationaleVascular smooth muscle cell (SMC) migration is an important pathological process in several vascular occlusive diseases, including atherosclerosis and restenosis, both of which are accelerated by diabetes mellitus.
objectiveTo determine the mechanisms of abnormal vascular SMC migration in type 2 diabetes, the obese Zucker rat (ZO), a model of obesity and insulin resistance, was studied. METHODS AND
resultsIn culture, ZO aortic SMCs showed a significant increase in Nox4 mRNA and protein levels compared with the control lean Zucker rat (ZL). The sarco-/endoplasmic reticulum Ca(2+) ATPase (SERCA) nitrotyrosine-294,295 and cysteine-674 (C674)-SO(3)H were increased in ZO SMCs, indicating oxidant stress. Unlike ZL SMC, nitric oxide (NO) failed to inhibit serum-induced SMC migration in ZO. Transfection of Nox4 small interference RNA or overexpression of SERCA2b wild type, but not C674S mutant SERCA, restored the response to NO. Knockdown of Nox4 also decreased SERCA oxidation in ZO SMCs. In addition, transforming growth factor-β1 via Smad2 was necessary and sufficient to upregulate Nox4, oxidize SERCA, and block the antimigratory action of NO in ZO SMCs. Corresponding to the results in cultured SMCs, immunohistochemistry confirmed that Nox4 and SERCA C674-SO(3)H were significantly increased in ZO aorta. After common carotid artery injury, knockdown of Nox4 by adenoviral Nox4 short hairpin RNA decreased Nox4 and SERCA C674-SO(3)H staining and significantly decreased injury-induced neointima.
conclusionThese studies indicate that the upregulation of Nox4 by transforming growth factor-β1 in ZO SMCs is responsible for the impaired response to NO by a mechanism involving the oxidation of SERCA C674. Knockdown of Nox4 inhibits oxidation of SERCA, as well as neointima formation, after ZO common carotid artery injury.
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