Prevention of salt-induced renal injury by activation of NAD(P)H: quinone oxidoreductase 1, associated with NADPH oxidase

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Title
Prevention of salt-induced renal injury by activation of NAD(P)H: quinone oxidoreductase 1, associated with NADPH oxidase
Author(s)
Yong Hoon KimJung Hwan HwangJung Ran Noh; Gil Tae Gang; S Tadi; Y H Yim; N H Jeong; T H Kwak; S H Lee; G R Kweon; J M Kim; M Shong; I K Lee; Chul Ho Lee
Bibliographic Citation
Free Radical Biology and Medicine, vol. 52, no. 5, pp. 880-888
Publication Year
2012
Abstract
NADPH oxidase (NOX) is a predominant source of reactive oxygen species (ROS), and the activity of NOX, which uses NADPH as a common rate-limiting substrate, is upregulated by prolonged dietary salt intake. β-Lapachone (βL), a well-known substrate of NAD(P)H:quinone oxidoreductase 1 (NQO1), decreases the cellular NAD(P)H/NAD(P) + ratio via activation of NQO1. In this study, we evaluated whether NQO1 activation by βL modulates salt-induced renal injury associated with NOX-derived ROS regulation in an animal model. Dahl salt-sensitive (DS) rats fed a high-salt (HS) diet were used to investigate the renoprotective effect of NQO1 activation. βL treatment significantly lowered the cellular NAD(P)H:NAD(P) + ratio and dramatically reduced NOX activity in the kidneys of HS diet-fed DS rats. In accordance with this, total ROS production and expression of oxidative adducts also decreased in the βL-treated group. Furthermore, HS diet-induced proteinuria and glomerular damage were markedly suppressed, and inflammation, fibrosis, and apoptotic cell death were significantly diminished by βL treatment. This study is the first to demonstrate that activation of NQO1 has a renoprotective effect that is mediated by NOX activity via modulation of the cellular NAD(P)H:NAD(P) + ratio. These results provide strong evidence that NQO1 might be a new therapeutic target for the prevention of salt-induced renal injury.
Keyword
β-LapachoneFree radicalsHigh-saltNADPH oxidaseNQO1Reactive oxygen species
ISSN
0891-5849
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.freeradbiomed.2011.12.007
Type
Article
Appears in Collections:
Ochang Branch Institute > Division of National Bio-Infrastructure > Laboratory Animal Resource & Research Center > 1. Journal Articles
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