PloS one, 2013-10, Vol.8 (10), p.e78626
2013
Details
- Autor(en) / Beteiligte
- Titel
- Circadian clock control of Nox4 and reactive oxygen species in the vasculature
- Ist Teil von
- PloS one, 2013-10, Vol.8 (10), p.e78626
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Link zum Volltext
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Recent studies have shown that circadian clock disruption is associated with pathological remodeling in the arterial structure and vascular stiffness. Moreover, chronic circadian disruption is associated with dysfunction in endothelial responses and signaling. Reactive oxygen species have emerged as key regulators in vascular pathology. Previously, we have demonstrated that circadian clock dysfunction exacerbates superoxide production through eNOS uncoupling. To date, the impact of circadian clock mutation on vascular NADPH oxidase expression and function is not known. The goal in the current study was to determine if the circadian clock controls vascular Nox4 expression and hydrogen peroxide formation in arteries, particularly in endothelial and vascular smooth muscle cells. In aorta, there was an increase in hydrogen peroxide and Nox4 expression in mice with a dysfunctional circadian rhythm (Bmal1-KO mice). In addition, the Nox4 gene promoter is activated by the core circadian transcription factors. Lastly, in synchronized cultured human endothelial cells, Nox4 gene expression exhibited rhythmic oscillations. These data reveal that the circadian clock plays an important role in the control of Nox4 and disruption of the clock leads to subsequent production of reaction oxygen species.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0078626Titel-ID: cdi_plos_journals_1445923193
- Format
- –
- Schlagworte
- Animals, Aorta, Aorta - metabolism, Aorta - physiology, ARNTL Transcription Factors - deficiency, ARNTL Transcription Factors - genetics, Arteries, Biology, BMAL1 protein, Circadian Clocks, Circadian rhythm, Circadian rhythms, Coronary vessels, Disruption, DNA binding proteins, Endothelial cells, Endothelium, Gene expression, Gene Expression Regulation, Gene Knockout Techniques, Genes, Genetic transcription, Growth factors, Humans, Hydrogen, Hydrogen peroxide, Hydrogen Peroxide - metabolism, Hypertension, Laboratory animals, Mice, Muscles, Mutation, NAD(P)H oxidase, NADPH Oxidase 4, NADPH Oxidases - genetics, NADPH Oxidases - metabolism, NOX4 gene, NOX4 protein, Oscillations, Oxidases, Oxygen, Pharmacology, Physiology, Promoter Regions, Genetic - genetics, Proteins, Reactive oxygen species, Reactive Oxygen Species - metabolism, Regulators, Rodents, Signal transduction, Signaling, Smooth muscle, Stiffness, Superoxide, Toxicology, Transcription factors