Regulation of Cytochrome P450 2E1 expression by ethanol: Role of oxidative stressmediated PKC/JNK/SP1 pathway

doi:10.4172/0975-0851.s1.015

Abstract

Highlights

The alcohol metabolism-mediated liver toxicity occurs through the formation of reactive oxygen species (ROS) and the reactive metabolite, acetaldehyde, which cause DNA damage and lipid and protein oxidations.[4]
As previously shown in U937 monocytic cells,[15] we examined whether ethanol induces ROS in SVGA astrocytes at 100 mM ethanol at 12–36 h
To examine whether CYP2E1 is responsible for the generation of ROS, we knocked down CYP2E1 expression through transfection using 10 nM predesigned CYP2E1 siRNA and 10 nM scrambled siRNA as control

Summary

Introduction

The alcohol metabolism-mediated liver toxicity occurs through the formation of reactive oxygen species (ROS) and the reactive metabolite, acetaldehyde, which cause DNA damage and lipid and protein oxidations.[4]. CYP2E1 is the only enzyme involved in the non-catalase oxidation of ethanol and ROS production.[10] Its induction leads to increased lipid peroxidation and apoptosis, Regulation of CYP2E1 by ethanol through PKC/JNK/SP1 M Jin et al resulting in increased permeability of the blood–brain barrier and neurodegeneration.[11] limited information is available on the role of CYP2E1 in ethanol-mediated effects on human astrocytes, which is the predominant cell type in the brain and its major role is to protect neuronal integrity.[12,13] Activated astrocytes, especially through increased oxidative stress by alcohol, may cause neuronal damage. In this study, we used human SVGA astrocytic and U937 monocytic cell lines to investigate the role of CYP2E1 in ethanol-mediated oxidative stress, apoptosis, cell death, and the mechanism by which ethanol regulates CYP2E1 expression

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Conclusion