Oligodendrocytes are the myelin-producing cells in the central nervous system. It was proposed that these cells are much more prone to oxidative damage than to other cells of the central nervous system. This fact seems to be due to their high iron store and low antioxidative defense mechanisms. Consequently, free radical induced damage should lead to an enhanced damage of oligodendrocytes. Thus, we chose the oligodendrocyte cell line OLN 93 to measure the stability of the protein pool after oxidation and the possibilities of protecting proteins by alpha-phenyl-N-tert-butylnitrone (PBN). We were able to demonstrate for the first time that OLN 93 cells are able to respond with an increase in overall proteolysis when exposed to various oxidants. This increase was the consequence of an enhanced protein oxidation. The activity of the 20S proteasome, which is thought to be involved in the removal of oxidized proteins, was not effected by moderate concentrations of the oxidants. The spin-trap PBN was used as an antioxidant and was able to prevent protein oxidation in OLN 93 cells effectively. Consequently, we proved that PBN is also able to prevent the increase in overall protein oxidation. We were able to demonstrate that OLN 93 oligodendrocytes react to oxidative stress with an increase in the protein turnover directed towards the removal of oxidized proteins. The intracellular spin-trap PBN is able to prevent protein oxidation in OLN 93 cells.