Myocyte enhancer factor 2B is involved in the inducible expression of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme
| Autor: | Masato, Katsuyama, Muhammer, Ozgur Cevik, Noriaki, Arakawa, Tomoko, Kakehi, Toru, Nishinaka, Kazumi, Iwata, Masakazu, Ibi, Kuniharu, Matsuno, Chihiro, Yabe-Nishimura |
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| Rok vydání: | 2007 |
| Předmět: |
Platelet-Derived Growth Factor
Transcriptional Activation DNA Complementary Base Sequence MEF2 Transcription Factors Molecular Sequence Data Electrophoretic Mobility Shift Assay Dinoprost Cell Line Rats Myogenic Regulatory Factors Superoxides Enzyme Induction NADPH Oxidase 1 Animals Blood Vessels NADH NADPH Oxidoreductases Amino Acid Sequence Gene Silencing RNA Messenger Promoter Regions Genetic DNA Primers |
| Zdroj: | The FEBS journal. 274(19) |
| ISSN: | 1742-464X |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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