Lipid constituents in oligodendroglial cells alter susceptibility to H2O2-induced apoptotic cell death via ERK activation

The present work examines the effect of membrane lipid composition on activ ation of extracellular signal-regulated protein kinases (ERK) and cell deat h following oxidative stress. When subjected to 50 muM docosahexaenoic acid (DHA, 22 : 6 n-3), cellular phospholipids of OLN 93 cells, a clonal line o f oligodendroglia origin low in DHA, were enriched with this polyunsaturate d fatty acid. In the presence of 1 mM N,N-dimethylethanolamine (dEa) a new phospholipid species analog was formed in lieu of phosphatidylcholine. Expo sure of DHA-enriched cells to 0.5 mM H2O2 caused sustained activation of ER K up to 24 h. At this time massive apoptotic cell death was demonstrated by ladder and TUNEL techniques. H2O2-induced stress applied to dEa or DHA/dEa co-supplemented cells showed only a transient ERK activation and no cell d eath after 24 h. Moreover, while ERK was rapidly translocated into the nucl eus in DHA-enriched cells, dEa supplements completely blocked ERK nuclear t ranslocation. This study suggests that H2O2-induced apoptotic cell death is associated with prolonged ERK activation and nuclear translocation in DHA- enriched OLN 93 cells, while both phenomena are prevented by dEa supplement s. Thus, the membrane lipid composition ultimately modulates ERK activation and translocation and therefore can promote or prevent apoptotic cell deat h.