Konsequenzen von oxidativem Stress auf oligodendrogliale Zellen

Abstract

Oligodendrocytes are the myelinating cells of the central nervous system. Due to their high metabolic activity and lipid content antioxidative defence mechanisms are essential, as oxidative stress is a hallmark of demyelinating diseases. The present work focussed on the investigation of protective mechanisms of oligodendroglial cells against oxidative stress and its impact on cellular metabolism using the oligodendroglial cell line OLN-93 and secondary oligodendrocytes. Peroxide detoxification capacities as well as cellular glutathione and iron contents of OLN-93 cells were determined and potential heat shock protein 27 (HSP27) mediated modulations of these were studied. The obtained data show that an over expression of HSP27 did not affect those components and might therefore not be associated with protection against oxidative stress in oligodendroglial cells. Fumaric acid esters are currently being investigated as therapeutic agents for multiple sclerosis in clinical studies. Fumaric acid dialkyl esters were shown to be non-toxic, but depleted the cellular glutathione content of both OLN-93 cells and secondary oligodendrocytes, probably by conjugate formation of glutathione with these substances or their metabolites. Cellular glutathione content was restored via new synthesis subsequent to treatment with fumaric acid dialkyl esters and was accompanied by induction of heme oxygenase 1. Studies on the long term effects of non-lethal peroxide treatment showed consequences in cellular glucose metabolism and resulted in a cell type specific increased lactate release by OLN-93 cells. As lactate is essential for neurons, an increased lactate release of oligodendroglial cells might hint at a protective mechanism for neurons under oxidative stress.