ArticleThe Journal of biological chemistry2016
Transcriptional Regulation of Cystathionine-γ-Lyase in Endothelial Cells by NADPH Oxidase 4-Dependent Signaling.
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 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 53 citations in OpenAlex.
- Review
- Redox Regulation of Endogenous Gasotransmitters in Vascular Health and Disease.International journal of molecular sciences · 2025Review
- Reactive Sulfur Species and Protein Persulfidation: An Emerging Redox Axis in Human Health and Disease.Current issues in molecular biology · 2025Review
- TET2 has endothelial-specific roles in interferon responses that are dysregulated by hyperglycemia in vitro and in vivo.The Journal of biological chemistry · 2025Article
- Cystathionine gamma-lyase-mediated hypoxia inducible factor 1-alpha expression drives clear cell ovarian cancer progression.The Journal of pathology · 2025Article
- Prolonged In Vivo Chemogenetic Generation of Hydrogen Peroxide by Endothelial Cells Induces Cardiac Remodelling and Vascular Dysfunction.Antioxidants (Basel, Switzerland) · 2025Article
- Asynchronous changes of hydrogen sulfide and its generating enzymes in most tissues with the aging process.Bioscience reports · 2024Article
- Why Is Iron Deficiency/Anemia Linked to Alzheimer's Disease and Its Comorbidities, and How Is It Prevented?Biomedicines · 2023Review
- The regulation of cardiac intermediary metabolism by NADPH oxidases.Cardiovascular research · 2023Review
- Pharmacological Inhibition of NOX4 Improves Mitochondrial Function and Survival in Human Beta-Cells.Biomedicines · 2021Article
- Synthesis of Reactive Sulfur Species in Cultured Vascular Endothelial Cells after Exposure to TGF-βInternational journal of molecular sciences · 2021Article
- Review
- Endothelium as a Source and Target of HAntioxidants (Basel, Switzerland) · 2021Review
- Estrogen Regulates Local Cysteine Metabolism in Mouse Myometrium.Reproductive sciences (Thousand Oaks, Calif.) · 2021Article
- Transcriptional Induction of Cystathionine γ-Lyase, a Reactive Sulfur-Producing Enzyme, by Copper Diethyldithiocarbamate in Cultured Vascular Endothelial Cells.International journal of molecular sciences · 2020Article
- Nrf2 Activation and Its Coordination with the Protective Defense Systems in Response to Electrophilic Stress.International journal of molecular sciences · 2020Review
- Shear stress regulates cystathionine γ lyase expression to preserve endothelial redox balance and reduce membrane lipid peroxidation.Redox biology · 2020Article
- Gasotransmitters in pregnancy: from conception to uterine involution.Biology of reproduction · 2019Review
- Oxidation of PKGIα mediates an endogenous adaptation to pulmonary hypertension.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Environmental Electrophile-Mediated Toxicity in Mice Lacking Nrf2, CSE, or Both.Environmental health perspectives · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
The gasotransmitter, hydrogen sulfide (H2S) is recognized as an important mediator of endothelial cell homeostasis and function that impacts upon vascular tone and blood pressure. Cystathionine-γ-lyase (CSE) is the predominant endothelial generator of H2S, and recent evidence suggests that its transcriptional expression is regulated by the reactive oxygen species, H2O2. However, the cellular source of H2O2 and the redox-dependent molecular signaling pathway that modulates this is not known. We aimed to investigate the role of Nox4, an endothelial generator of H2O2, in the regulation of CSE in endothelial cells. Both gain- and loss-of-function experiments in human endothelial cells in vitro demonstrated Nox4 to be a positive regulator of CSE transcription and protein expression. We demonstrate that this is dependent upon a heme-regulated inhibitor kinase/eIF2α/activating transcription factor 4 (ATF4) signaling module. ATF4 was further demonstrated to bind directly to cis-regulatory sequences within the first intron of CSE to activate transcription. Furthermore, CSE expression was also increased in cardiac microvascular endothelial cells, isolated from endothelial-specific Nox4 transgenic mice, compared with wild-type littermate controls. Using wire myography we demonstrate that endothelial-specific Nox4 transgenic mice exhibit a hypo-contractile phenotype in response to phenylephrine that was abolished when vessels were incubated with a CSE inhibitor, propargylglycine. We, therefore, conclude that Nox4 is a positive transcriptional regulator of CSE in endothelial cells and propose that it may in turn contribute to the regulation of vascular tone via the modulation of H2S production.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.