NADPH oxidase is the major source of superoxide production in cardiovascular tissues. We and others reported that PG (prostaglandin) F2α, PDGF (platelet-derived growth factor) and angiotensin II cause hypertrophy of vascular smooth muscle cells by induction of NOX1 (NADPH oxidase 1), a catalytic subunit of NADPH oxidase. We found DPI (diphenylene iodonium), an inhibitor of flavoproteins, including NADPH oxidase itself, almost completely suppressed induction of NOX1 mRNA by PGF2α or PDGF in a rat vascular smooth muscle cell line, A7r5. Exploration into the site of action of DPI using various inhibitors suggested the involvement of mitochondrial oxidative phosphorylation in PGF2α- or PDGF-induced increase in NOX1 mRNA. In a luciferase reporter assay, activation of the CRE (cAMP-response element)-dependent gene transcription by PGF2α was attenuated by oligomycin, an inhibitor of mitochondrial FoF1-ATPase. Oligomycin and other mitochondrial inhibitors also suppressed PGF2α-induced phosphorylation of ATF (activating transcription factor)-1, a transcription factor of the CREB (CRE-binding protein)/ATF family. Silencing of the ATF-1 gene by RNA interference significantly reduced the induction of NOX1 by PGF2α or PDGF, while overexpression of ATF-1 recovered NOX1 induction suppressed by oligomycin. Taken together, ATF-1 may play a pivotal role in the up-regulation of NOX1 in rat vascular smooth muscle cells.
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Research Article|
February 22 2005
Essential role of ATF-1 in induction of NOX1, a catalytic subunit of NADPH oxidase: involvement of mitochondrial respiratory chain
Masato KATSUYAMA;
Masato KATSUYAMA
*Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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ChunYuan FAN;
ChunYuan FAN
*Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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Noriaki ARAKAWA;
Noriaki ARAKAWA
*Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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Toru NISHINAKA;
Toru NISHINAKA
*Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
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Makoto MIYAGISHI;
Makoto MIYAGISHI
†Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan
‡Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba Science City 305-8562, Japan
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Kazunari TAIRA;
Kazunari TAIRA
†Department of Chemistry and Biotechnology, School of Engineering, The University of Tokyo, Tokyo 113-8656, Japan
‡Gene Function Research Center, National Institute of Advanced Industrial Science and Technology, Tsukuba Science City 305-8562, Japan
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Chihiro YABE-NISHIMURA
Chihiro YABE-NISHIMURA
1
*Department of Pharmacology, Kyoto Prefectural University of Medicine, Kyoto 602-8566, Japan
1To whom correspondence should be addressed to (email nchihiro@koto.kpu-m.ac.jp).
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Publisher: Portland Press Ltd
Received:
July 12 2004
Revision Received:
September 14 2004
Accepted:
October 18 2004
Accepted Manuscript online:
October 18 2004
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 386 (2): 255–261.
Article history
Received:
July 12 2004
Revision Received:
September 14 2004
Accepted:
October 18 2004
Accepted Manuscript online:
October 18 2004
Citation
Masato KATSUYAMA, ChunYuan FAN, Noriaki ARAKAWA, Toru NISHINAKA, Makoto MIYAGISHI, Kazunari TAIRA, Chihiro YABE-NISHIMURA; Essential role of ATF-1 in induction of NOX1, a catalytic subunit of NADPH oxidase: involvement of mitochondrial respiratory chain. Biochem J 1 March 2005; 386 (2): 255–261. doi: https://doi.org/10.1042/BJ20041180
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