Alpha, beta-unsaturated aldehydes mediate inducible expression of glutathione S-transferase in hepatoma cells through activation of the antioxidant response element (ARE).

Abstract

It is well established that during oxidative stress highly reactive, a,β-unsaturated aldehydes are prced from the β-scission of lipid alkoxy radicals formed from the reaction of carbon-centered radicals with molecular oxygen (Esterbauer et al, 1991; Schauer et al990). Four-hydroxynonenal (4-HNE) and other endogenous and exogenous aldehydes, such as malondialdehyde and acrolein, are also generated in response to a variety of oxidative stimuli including free intracellular iron (Fe2+) (Esterbauer et al, 1991), chronic ethanol (Ingelman-Sundberg and Johansson, 1984), and exposure to halogenated hydrocarbons (Poli et, 1985). The a,β-unsaturated configuration of these compounds allows them to undergo Michael addition chemistry resulting in the formation of covalent adducts with DNA and protein nucleophiles. The potential of these electrophilic aldehydes to target specific cellular nucelophiles is consistent with the deleterious effects of 4-HNE which includes inhibition of protein synthesis (White and Rees, 1984), disruption of Ca2+ homeostasis (Schauet al, 1990), and neutrophil chemotaxis (Curzio et al, 1987)