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Biochem Biophys Res Commun. 2008 Sep 19;374(2):351-5. doi: 10.1016/j.bbrc.2008.07.027. Epub 2008 Jul 16.

The AP-1 site is essential for the promoter activity of NOX1/NADPH oxidase, a vascular superoxide-producing enzyme: Possible involvement of the ERK1/2-JunB pathway.

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1
Department of Pharmacology, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto 602-8566, Japan.

Abstract

NADPH oxidase is a major source of the superoxide produced in cardiovascular tissues. The 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). It was reported previously that the inducible expression of NOX1 is governed by the activating transcription factor-1 (ATF-1)-myocyte enhancer factor 2B (MEF2B) cascade downstream of phosphoinositide 3 (PI3) kinase. It was also reported that extracellular signal-regulated kinase (ERK) 1/2 is involved in the expression of NOX1. To further clarify the factors involved in NOX1 induction downstream of ERK1/2, the promoter region of the NOX1 gene was analyzed. A consensus activator protein-1 (AP-1) site was found at -98/-92 in the 5'-flanking region of the rat NOX1 gene. The introduction of mutations at this site abolished PGF(2alpha)-induced transcriptional activation in a luciferase assay. Electrophoresis mobility shift assays demonstrated that PGF(2alpha) and PDGF augmented the binding of JunB to this sequence. PD98059, an inhibitor of MAPK/ERK kinase, suppressed the expression of JunB induced by PGF(2alpha) or PDGF. These results suggest that the ERK1/2-JunB pathway is a key regulator of the inducible expression of the NOX1 gene in vascular smooth muscle cells.

PMID:
18638447
DOI:
10.1016/j.bbrc.2008.07.027
[Indexed for MEDLINE]

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