Role of NAD(P)H : quinone oxidoreductase 1 on tumor necrosis factor-alpha-induced migration of human vascular smooth muscle cells
- Authors
- Lee, SO[Lee, Syng-Ook]; Chang, YC[Chang, Young-Chae]; Whang, K[Whang, Key]; Kim, CH[Kim, Cheorl-Ho]; Lee, IS[Lee, In-Seon]
- Issue Date
- 1-Nov-2007
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- vascular smooth muscle cells; migration; TNF-alpha; NAD(P)H : quinone oxidoreductase 1; dicumarol; matrix metalloproteinase-9
- Citation
- CARDIOVASCULAR RESEARCH, v.76, no.2, pp.331 - 339
- Indexed
- SCIE
SCOPUS
- Journal Title
- CARDIOVASCULAR RESEARCH
- Volume
- 76
- Number
- 2
- Start Page
- 331
- End Page
- 339
- URI
- https://scholarworks.bwise.kr/skku/handle/2021.sw.skku/83598
- DOI
- 10.1016/j.cardiores.2007.06.030
- ISSN
- 0008-6363
- Abstract
- Objectives: In a preliminary study, NAD(P)H:quinone oxidoreductase 1 (NQO1) was found to be highly expressed in cultured human aortic smooth muscle cells (HASMC) and dicumarol, a NQO1 inhibitor and a coumarin-derived natural anticoagulant, suppressed tumor necrosis factor (TNF)-alpha-induced HASMC migration. Therefore, it was hypothesized that NQO1 plays an important role in the regulation of vascular smooth muscle cells (VSMC) migration activated by TNF-alpha. Methods and results: Gelatin zymography, reporter gene, electrophoretic mobility shift and Western blotting assays showed that dicumarol, but not other coumarin-derived anticoagulants, inhibited TNF-alpha-induced HASMC migration and suppressed TNF-a-induced matrix metalloproteinase (MW)-9 expression and secretion in a dose-dependent manner. In addition, down-regulation of NQO1 by transfection of its small interfering RNA similarly inhibited TNF-alpha-induced MMP-9 secretion, indicating that dicumarol-mediated inhibition of MMP-9 expression is due in large part to inhibition of NQO1. Down-regulation of NQO1 inhibits MMP-9 gene expression by suppressing activation of nuclear factor-kappa B (NF-KB) and activator protein-1 (AP-1), well-known key elements mediating MMP-9 gene expression in its promoter, via the p38 MAPK and JNK pathways. Conclusion: The results of the present study demonstrate that down-regulation of NQO1 effectively suppresses TNF-alpha-induced HASMC migration through inhibition of MMP-9 expression, suggesting that NQO1 may be a potential target for the prevention of vascular disorders related to migration of VSMC. (C) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.
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Collections - Science > Department of Biological Science > 1. Journal Articles
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