Role of Oxidative Stress in Adaptive Responses in Special Reference to Atherogenesis

Abstract

Although lipid peroxidation products have been implicated in oxidative stress-related diseases, pretreatment of cells with such compounds at sublethal concentrations shows significant cytoprotective effects against forthcoming oxidative stress. The adaptive response induced by 4-hydroxynonenal (HNE) is critically mediated by gene expression of cytoprotective proteins via NF-E2-related factor 2/Kelch-like-ECH-associated protein 1 (Nrf2/Keap-1) pathway. The physical or mechanical stimuli such as shear stress also impose adaptive responses by inducing gene expression. Laminar shear stress, anti-atherogenic shear stress activates Nrf2/Keap-1 pathway. The transcriptome analysis using DNA microarray reveal high similarity in gene expression profiles of cells treated with HNE and laminar shear stress, providing insight into molecular mechanisms. These findings suggest a general hormetic effect of diverse stimuli in cell cultures and may lead to a reappraisal of the eventual role of reactive oxygen species and lipid peroxidation in organisms.