Transactivation of the EGF receptor and a PI3 kinase-ATF-1 pathway is involved in the upregulation of NOX1, a catalytic subunit of NADPH oxidase.
We previously reported that hypertrophy of vascular smooth muscle cells caused by prostaglandin (PG) F2alpha is mediated by the induction of NOX1, a catalytic subunit of NADPH oxidase that generates superoxide. The signal transduction pathway(s) involved in this process, however, remained unresolved. PGF2alpha enhanced the phosphorylation of the epidermal growth factor (EGF) receptor, and a selective inhibitor of EGF receptor kinase, tyrphostin AG1478, significantly suppressed PGF2alpha-induced NOX1 expression. AG1478 also blunted the PGF2alpha-induced phosphorylation of extracellular signal-regulated protein kinase (ERK)1/2 and Akt. Phosphoinositide 3 (PI3) kinase inhibitors not only reduced PGF2alpha-induced NOX1 expression, but also suppressed the phosphorylation of ATF-1, a transcription factor previously shown to play a key role in the induction of NOX1. Accordingly, the transactivation of the EGF receptor and the activation of ERK1/2, PI3 kinase, and ATF-1 constitute the signaling pathways involved in the upregulation of NOX1.
Fan
Chunyuan
C
Department of Pharmacology, Kyoto Prefectural University of Medicine, Kawaramachi-Hirokoji, Kamigyo-Ku, Kyoto 602-8566, Japan.
Katsuyama
Masato
M
Nishinaka
Toru
T
Yabe-Nishimura
Chihiro
C
D051697:Activating Transcription Factor 1; D000818:Animals; D002384:Catalysis; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D015237:Dinoprost / Q000494:pharmacology; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D009247:NADH, NADPH Oxidoreductases / Q000235:genetics / Q000378:metabolism*; D000074624:NADPH Oxidase 1; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation / Q000187:drug effects; D015854:Up-Regulation
D051697:Activating Transcription Factor 1; D004268:DNA-Binding Proteins; D015237:Dinoprost; D066246:ErbB Receptors; D020782:Matrix Metalloproteinases; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020929:Mitogen-Activated Protein Kinase Kinases; D009247:NADH, NADPH Oxidoreductases; D000074624:NADPH Oxidase 1; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors; D047428:Protein Kinase Inhibitors; D021122:Protein Subunits; D012333:RNA, Messenger; D014157:Transcription Factors; C000614712:NOX1 protein, rat