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Title: Molecular structure and transcriptional regulation by nuclear factor-kappa B of the mouse kinin B-1 receptor gene
Authors: Merino, V. F.
Silva, J. A.
Araujo, R. C.
Avellar, MCW
Bascands, J. L.
Schanstra, J. P.
Paiva, ACM
Bader, M.
Pesquero, J. B.
Universidade Federal de São Paulo (UNIFESP)
Univ Mogi Cruzes
CHU Rangueil
Max Delbruck Ctr Mol Med
Keywords: enhancer
lipopolysaccharide (LPS)
mouse kinin B
receptor gene
multiple transcription start sites
nuclear factor-kappa B (NF-kappa B)
Issue Date: 1-Jun-2005
Publisher: Walter de Gruyter & Co
Citation: Biological Chemistry. Berlin: Walter de Gruyter & Co, v. 386, n. 6, p. 515-522, 2005.
Abstract: Kinins are important mediators in cardiovascular homeostasis, inflammation, and nociception. Two kinin receptors have been described, B-1 and B-2. the B-1 receptor is normally absent in healthy tissues, but is highly induced under pathological conditions. To understand the molecular mechanism of B-1 receptor up-regulation, we determined the mouse B-1 receptor gene structure, isolated and characterized the promoter region and studied its transcriptional regulation. the mouse B-1 receptor gene contains two exons (with the entire coding region located in the second exon) and a TATA-less promoter with multiple transcription start sites. A 7.7-kbp portion of the 5'-flanking region was examined for promoter activity in vascular smooth muscle cells (VSMCs). A minimal 92-bp fragment, located immediately upstream of the transcription start region, exerted basal and lipopolysaccharide (LPS)-inducible transcription activity in the sense and antisense orientation, and was thereby identified as an enhancer element. Nuclear extracts from VSMCs showed basal and LPS-inducible binding activity of nuclear factor (NF)-kappa B at this sequence. B-1 receptor transcription activation in response to LPS was abolished by cotransfection with I kappa B alpha Delta N, an NF-kappa B repressor. in summary, our results reveal the structure of the mouse B-1 receptor gene and the involvement of NF-kappa B in the inducible mouse kinin B-1 receptor expression under pathological conditions.
ISSN: 1431-6730
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