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Title 

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

Authors 

Yong Hoon KimJung Hwan HwangJung Ran NohGil Tae GangS TadiY H YimN H JeongT H KwakS H LeeG R KweonJ M KimM ShongI K LeeChul Ho Lee

Publisher 

Elsevier

Issue Date 

2012

Citation 

Free Radical Biology and Medicine, vol. 52, no. 5, pp. 880-888

Keywords 

β-LapachoneFree radicalsHigh-saltNADPH oxidaseNQO1Reactive oxygen species

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.

ISSN 

0891-5849

Link 

http://dx.doi.org/10.1016/j.freeradbiomed.2011.12.007

Appears in Collections

1. Journal Articles > Journal Articles

Registered Date

2019-05-02


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