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 activation of extracellular signal-regulated protein kinases (ERK) and cell death following oxidative stress. When subjected to 50 microM docosahexaenoic acid (DHA, 22 : 6 n-3), cellular phospholipids of OLN 93 cells, a clonal line of oligodendroglia origin low in DHA, were enriched with this polyunsaturated fatty acid. In the presence of 1 mM N,N-dimethylethanolamine (dEa) a new phospholipid species analog was formed in lieu of phosphatidylcholine. Exposure of DHA-enriched cells to 0.5 mM H2O2, caused sustained activation of ERK 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 death after 24 h. Moreover, while ERK was rapidly translocated into the nucleus in DHA-enriched cells, dEa supplements completely blocked ERK nuclear translocation. 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 supplements. Thus, the membrane lipid composition ultimately modulates ERK activation and translocation and therefore can promote or prevent apoptotic cell death.
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Department of Neurobiology and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
Gil
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Seger
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Yavin
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D017209:Apoptosis / Q000502:physiology*; D001692:Biological Transport / Q000502:physiology; D002070:Butadienes / Q000494:pharmacology; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D002467:Cell Nucleus / Q000201:enzymology; D003642:Deanol / Q000494:pharmacology; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004351:Drug Resistance; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D008055:Lipids / Q000502:physiology*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009570:Nitriles / Q000494:pharmacology; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress; D013997:Time Factors
D002070:Butadienes; D004791:Enzyme Inhibitors; D008055:Lipids; D009570:Nitriles; D016877:Oxidants; C113580:U 0126; D004281:Docosahexaenoic Acids; D003642:Deanol; D006861:Hydrogen Peroxide; D020928:Mitogen-Activated Protein Kinases