RGD Reference Report - Myocyte enhancer factor 2B is involved in the inducible expression of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme. - Rat Genome Database

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Myocyte enhancer factor 2B is involved in the inducible expression of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme.

Authors: Katsuyama, M  Ozgur Cevik, M  Arakawa, N  Kakehi, T  Nishinaka, T  Iwata, K  Ibi, M  Matsuno, K  Yabe-Nishimura, C 
Citation: Katsuyama M, etal., FEBS J. 2007 Oct;274(19):5128-36. Epub 2007 Sep 5.
RGD ID: 2316014
Pubmed: PMID:17822438   (View Abstract at PubMed)
DOI: DOI:10.1111/j.1742-4658.2007.06034.x   (Journal Full-text)

NADPH oxidase is a major source of the superoxide produced in cardiovascular tissues. Expression of NOX1, a catalytic subunit of NADPH oxidase, is induced by various vasoactive factors, including angiotensin II, prostaglandin (PG) F(2alpha) and platelet-derived growth factor (PDGF). To clarify the molecular basis of this transcriptional activation, we delineated the promoter region of the NOX1 gene. RT-PCR and 5'-rapid amplification of cDNA ends-based analyses revealed a novel 5'-terminal exon of the rat NOX1 gene located approximately 28 kb upstream of the exon containing the start codon. Both PGF(2alpha) and PDGF enhanced the transcriptional activity of the - 3.6 kb 5'-flanking region of the NOX1 gene in A7r5 cells, a rat vascular smooth muscle cell line. A PGF(2alpha)-response element was located between -146 and -125 in the 5'-flanking region containing a consensus binding site for myocyte enhancer factor 2 (MEF2), to which binding of MEF2 was augmented by PGF(2alpha). Gene silencing of MEF2B by RNA interference significantly suppressed the expression of NOX1, while silencing of activating transcription factor (ATF)-1, previously implicated in up-regulation of NOX1, abolished the PGF(2alpha)- or PDGF-induced expression of MEF2B. These results indicate that superoxide production in vascular smooth muscle cells is regulated by the ATF-1-MEF2B cascade by induction of the expression of the NOX1 gene.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of transcription by RNA polymerase II  IMP 2316014 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Atf1  (activating transcription factor 1)


Additional Information