Octadecaneuropeptide ODN prevents hydrogen peroxide-induced oxidative damage of biomolecules in cultured rat astrocytes

Abstract

Oxidative stress, associated with a variety of disorders including neurodegenerative diseases, is a major cause of cellular dysfunction and biomolecule damages which play a crucial role in neuronal apoptosis. Astrocytes specifically synthesize and release endozepines, a family of regulatory peptides, including the octadecaneuropeptide ODN. We have recently shown that ODN is a potent glioprotective agent that prevents hydrogen peroxide (H2O2)-induced oxidative stress and apoptosis. The purpose of the present study was to investigate the potential protective effect of ODN on oxidative-generated damage of biomolecules in cultured rat astrocytes. Incubation of cells with subnanomolar concentrations of ODN (0.1fM-0.1nM) inhibited H2O2-evoked reactive oxygen species accumulation and cell death in a concentration-dependent manner. Exposure of H2O2-treated cells to 0.1nM ODN inhibited superoxide anion generation and blocked oxidative damage of cell molecules caused by H2O2i.e. formation and accumulation of lipid oxidation products, malondialdehydes and conjugated dienes, and protein carbonyl compounds. Taken together, these data demonstrate for the first time that ODN prevents oxidative stress-induced alteration of cellular constituents. ODN is thus a potential candidate to reduce neuronal damage in various pathological conditions involving oxidative neurodegeneration.

Keywords: Astrocytes; Cell death; Lipid peroxidation; Octadecaneuropeptide; Oxidative stress; Protein carbonylation.