tailieunhanh - Báo cáo khoa học: Myocyte enhancer factor 2B is involved in the inducible expression of NOX1⁄ NADPH oxidase, a vascular superoxide-producing enzyme

NADPH oxidase is a major source of the superoxide produced in cardio-vascular tissues. Expression of NOX1, a catalytic subunit of NADPH oxi-dase, is induced by various vasoactive factors, including angiotensin II, prostaglandin (PG) F2a and platelet-derived growth factor (PDGF). To clarify the molecular basis of this transcriptional activation, we delineated the promoter region of the NOX1gene. | ễFEBS Journal Myocyte enhancer factor 2B is involved in the inducible expression of NOX1 NADPH oxidase a vascular superoxide-producing enzyme Masato Katsuyama Muhammer Ozgur Cevik Noriaki Arakawa Tomoko Kakehi Toru Nishinaka Kazumi Iwata Masakazu Ibi Kuniharu Matsuno and Chihiro Yabe-Nishimura Department of Pharmacology Kyoto Prefectural University of Medicine Japan Keywords activating transcription factor-1 myocyte enhancer factor 2 NADPH oxidase NOX1 vascular smooth muscle cells Correspondence C. Yabe-Nishimura Department of Pharmacology Kyoto PrefecturalUniversity of Medicine Kyoto 602-8566 Japan Fax 81 75 251 5348 Tel 81 75 251 5333 E-mail nchihiro@ These authors contributed equally to this work Received 2 June 2007 revised 26 July 2007 accepted 7 August 2007 doi 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 F2a 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 PGF2a and PDGF enhanced the transcriptional activity of the - kb 5 -flanking region of the NOX1 gene in A7r5 cells a rat vascular smooth muscle cell line. A PGF2a-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 PGF2a. 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 PGF2a- or