Brand A, Gil S, Seger R, Yavin E
Department of Neurobiology and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
J Neurochem. 2001 Feb;76(3):910-8. doi: 10.1046/j.1471-4159.2001.00085.x.
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.
本研究探讨了膜脂成分对氧化应激后细胞外信号调节蛋白激酶（ERK）激活及细胞死亡的影响。当用50微摩尔二十二碳六烯酸（DHA，22:6 n-3）处理时，少突胶质细胞来源的克隆细胞系OLN 93细胞（DHA含量低）的细胞磷脂富含这种多不饱和脂肪酸。在1毫摩尔N,N-二甲基乙醇胺（dEa）存在的情况下，形成了一种新的磷脂类似物来替代磷脂酰胆碱。将富含DHA的细胞暴露于0.5毫摩尔过氧化氢中，可导致ERK持续激活长达24小时。此时，通过梯状条带和TUNEL技术证实了大量凋亡性细胞死亡。施加于dEa或DHA/dEa共同补充细胞的过氧化氢诱导应激仅显示ERK短暂激活，24小时后无细胞死亡。此外，虽然在富含DHA的细胞中ERK迅速转运至细胞核，但dEa补充剂完全阻断了ERK的核转运。本研究表明，过氧化氢诱导的凋亡性细胞死亡与富含DHA的OLN 93细胞中ERK的长期激活和核转运有关，而这两种现象均可被dEa补充剂阻止。因此，膜脂成分最终调节ERK的激活和转运，进而可促进或预防凋亡性细胞死亡。
