Cdc42-Dependent Activation of NADPH Oxidase Is Involved in Ethanol-Induced Neuronal Oxidative Stress

Authors

Xin Wang, University of KentuckyFollow
Zunji Ke, University of Kentucky
Gang Chen, University of KentuckyFollow
Mei Xu, University of KentuckyFollow
Kimberly A. Bower, University of KentuckyFollow
Jacqueline A. Frank, University of KentuckyFollow
Zhuo Zhang, University of KentuckyFollow
Xianglin Shi, University of KentuckyFollow
Jia Luo, University of KentuckyFollow

Abstract

It has been suggested that excessive reactive oxygen species (ROS) and oxidative stress play an important role in ethanol-induced damage to both the developing and mature central nervous system (CNS). The mechanisms underlying ethanol-induced neuronal ROS, however, remain unclear. In this study, we investigated the role of NADPH oxidase (NOX) in ethanol-induced ROS generation. We demonstrated that ethanol activated NOX and inhibition of NOX reduced ethanol-promoted ROS generation. Ethanol significantly increased the expression of p47^phox and p67^phox, the essential subunits for NOX activation in cultured neuronal cells and the cerebral cortex of infant mice. Ethanol caused serine phosphorylation and membrane translocation of p47^phox and p67^phox, which were prerequisites for NOX assembly and activation. Knocking down p47^phox with the small interfering RNA was sufficient to attenuate ethanol-induced ROS production and ameliorate ethanol-mediated oxidative damage, which is indicated by a decrease in protein oxidation and lipid peroxidation. Ethanol activated cell division cycle 42 (Cdc42) and overexpression of a dominant negative (DN) Cdc42 abrogate ethanol-induced NOX activation and ROS generation. These results suggest that Cdc42-dependent NOX activation mediates ethanol-induced oxidative damages to neurons.

Document Type

Article

Publication Date

5-25-2012

Notes/Citation Information

Published in PLoS One, v. 7, no. 5, p. 38075.

© 2012 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1371/journal.pone.0038075

Repository Citation

Wang, Xin; Ke, Zunji; Chen, Gang; Xu, Mei; Bower, Kimberly A.; Frank, Jacqueline A.; Zhang, Zhuo; Shi, Xianglin; and Luo, Jia, "Cdc42-Dependent Activation of NADPH Oxidase Is Involved in Ethanol-Induced Neuronal Oxidative Stress" (2012). Pharmacology and Nutritional Sciences Faculty Publications. 3.
https://uknowledge.uky.edu/pharmacol_facpub/3