Positive regulation of NADPH oxidase 5 by proinflammatory-related mechanisms in human aortic smooth muscle cells

Free Radical Biology & Medicine
Adrian ManeaMonica Raicu

Abstract

NADPH oxidase Nox5 subtype expression is significantly increased in vascular smooth muscle cells (SMCs) underlying fibro-lipid atherosclerotic lesions. The mechanisms that up-regulate Nox5 are not understood. Consequently, we characterized the promoter of the human Nox5 gene and investigated the role of various proinflammatory transcription factors in the regulation of Nox5 in human aortic SMCs. The Nox5 promoter was cloned in the pGL3 basic reporter vector. Functional analysis was done employing 5' deletion mutants to identify the sequences necessary to effect high levels of expression in SMCs. Transcriptional initiation site was detected by rapid amplification of the 5'-cDNA ends. In silico analysis indicated the existence of typical NF-kB, AP-1, and STAT1/STAT3 sites. Transient overexpression of p65/NF-kB, c-Jun/AP-1, or STAT1/STAT3 increased significantly the Nox5 promoter activity. Chromatin immunoprecipitation demonstrated the physical interaction of c-Jun/AP-1 and STAT1/STAT3 proteins with the Nox5 promoter. Lucigenin-enhanced chemiluminescence, real-time PCR, and Western blot assays showed that pharmacological inhibition and the silencing of p65/NF-kB, c-Jun/AP-1, or STAT1/STAT3 reduced significantly the interferon γ-in...Continue Reading

References

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Citations

Sep 17, 2013·PLoS Pathogens·Lindsey S GarverCarolina Barillas-Mury
Apr 23, 2013·Antioxidants & Redox Signaling·Augusto C Montezano, Rhian M Touyz
Apr 2, 2014·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Stephen P Gray, Karin Jandeleit-Dahm
Jun 20, 2012·Journal of Cardiovascular Translational Research·Mona SedeekRhian M Touyz
May 7, 2014·Journal of Cellular and Molecular Medicine·Simona-Adriana ManeaAdrian Manea
Apr 15, 2015·Biochemical and Biophysical Research Communications·Adrian ManeaMaya Simionescu
Apr 14, 2015·Oxidative Medicine and Cellular Longevity·Ida Perrotta, Saveria Aquila
Feb 22, 2018·Laboratory Investigation; a Journal of Technical Methods and Pathology·Brittany G Durgin, Adam C Straub
Apr 9, 2013·Circulation·Stephen P GrayKarin A Jandeleit-Dahm
Oct 20, 2018·Antioxidants & Redox Signaling·Rhian M TouyzAugusto C Montezano
Nov 22, 2014·Current Opinion in Nephrology and Hypertension·Chet E HoltermanChristopher R J Kennedy
May 6, 2017·Clinical Science·Jay C JhaKarin Jandeleit-Dahm
Nov 1, 2018·Physiological Reviews·Jesús TejeroMark T Gladwin
Feb 26, 2019·Experimental Physiology·Rhian M TouyzLivia L Camargo
Sep 20, 2020·The International Journal of Biochemistry & Cell Biology·Javier MarquésGuillermo Zalba

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