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

Xin Wang; Zunji Ke; Gang Chen; Mei Xu; Kimberly A Bower; Jacqueline A Frank; Zhuo Zhang; Xianglin Shi; Jia Luo

doi:10.1371/journal.pone.0038075

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

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

Xin Wang, Zunji Ke, Gang Chen, Mei Xu, Kimberly A Bower, Jacqueline A Frank, Zhuo Zhang, Xianglin Shi and Jia Luo

PloS one, Vol.7(5), pp.e38075-e38075

05/25/2012

DOI: 10.1371/journal.pone.0038075

PMCID: PMC3360628

PMID: 22662267

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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.

Biology

Medicine

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Title: Subtitle: Cdc42-Dependent Activation of NADPH Oxidase Is Involved in Ethanol-Induced Neuronal Oxidative Stress
Creators: Xin Wang - University of Kentucky
Zunji Ke - University of Kentucky
Gang Chen - University of Kentucky
Mei Xu - University of Kentucky
Kimberly A Bower - University of Kentucky
Jacqueline A Frank - University of Kentucky
Zhuo Zhang - University of Kentucky
Xianglin Shi - University of Kentucky
Jia Luo - University of Kentucky
Resource Type: Journal article
Publication Details: PloS one, Vol.7(5), pp.e38075-e38075
DOI: 10.1371/journal.pone.0038075
PMID: 22662267
PMCID: PMC3360628
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science
Alternative title: Ethanol Induces Cdc42-Dependent Activation of NOX
Language: English
Date published: 05/25/2012
Academic Unit: Pathology
Record Identifier: 9984201118002771

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