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Dadun > Depósito Académico > CIMA (Centro de Investigación Médica Aplicada) > Área de Ciencias Cardiovasculares > Enfermedad vascular hipertensiva > DA - CIMA - Cardiovasculares - Enfermedad vascular - Artículos de Revista >

Polymorphisms and promoter overactivity of the p22(phox) gene in vascular smooth muscle cells from spontaneously hypertensive rats
Authors: Zalba, G. (Guillermo)
San-Jose, G. (Gorka)
Beaumont, F.J. (F. J.)
Fortuño, M.A. (María Antonia)
Fortuño, A. (A.)
Diez, J. (Javier)
Keywords: NADH/NADPH oxidase
Gene promoter
Vascular smooth muscle cells
Superoxide anion
Issue Date: 2001
Publisher: American Heart Association
Publisher version: http://circres.ahajournals.org/cgi/content/full/88/2/217
ISSN: 1524-4571
Citation: Zalba G, San José G, Beaumont FJ, Fortuño MA, Fortuño A, Díez J. Polymorphisms and promoter overactivity of the p22(phox) gene in vascular smooth muscle cells from spontaneously hypertensive rats. Circ Res 2001 Feb 2;88(2):217-222.
Abstract
In a previous study, we found that the p22(phox) subunit of the NADH/NADPH oxidase is overexpressed in vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats (SHRs) with enhanced vascular production of superoxide anion ((.)O(2)(-)). Thus, we have investigated whether changes in the sequence or activity of the promoter region of p22(phox) gene are present in SHRs. To carry out this analysis, first of all, we characterized the rat gene structure and promoter region for the p22(phox) subunit. The p22(phox) gene spans approximately 10 kb and contains 6 exons and 5 introns. Primer extension analysis indicated the transcriptional start site 100 bp upstream from the translational start site. The immediate promoter region of the p22(phox) gene does not contain a TATA box, but there are a CCAC box and putative recognition sites for nuclear factors, such as SP1, gamma-interferon, and nuclear factor-kappaB. Using reporter-gene transfection analysis, we found that this promoter was functional in VSMCs. Furthermore, we observed that p22(phox) promoter activity was significantly higher in VSMCs from SHRs than from normotensive Wistar-Kyoto rats. In addition, we found that there were 5 polymorphisms in the sequence of p22(phox) promoter between Wistar-Kyoto rats and SHRs and that they were functional. The results obtained in this study provide a tool to explore the mechanisms that regulate the expression of p22(phox) gene in rat VSMCs. Furthermore, our findings show that changes in the sequence of p22(phox) gene promoter and in the degree of activation of VSMCs are responsible for upregulated expression of p22(phox) in SHRs.
Permanent link: http://hdl.handle.net/10171/17840
Appears in Collections:DA - CIMA - Servicios de apoyo - Biobanco - Artículos de revista
DA - CIMA - Cardiovasculares - Cardiopatía hipertensiva - Artículos de Revista
DA - CIMA - Cardiovasculares - Enfermedad vascular - Artículos de Revista

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