Heimli H, Finstad H S, Drevon C A
Institute for Nutrition Research, University of Oslo, Norway.
Lipids. 2001 Jun;36(6):613-21. doi: 10.1007/s11745-001-0765-x.
The present study is focused on the role of oxidative stress in the induction of either necrosis or apoptosis by eicosapentaenoic acid (EPA) in the lymphoma cell lines Raji and Ramos, respectively. To investigate the different death modes induced by EPA, we assessed the importance of some antioxidants and reactive oxygen species in the two cell lines. We observed that different antioxidants counteracted the necrotic effect of EPA on Raji cells to a different extent, and that vitamin E counteracted EPA-induced accumulation of superoxide anion in this cell line. On the contrary, no effects of antioxidants were observed on development of apoptosis induced by EPA in Ramos cells, and vitamin E did not counteract EPA-induced accumulation of superoxide anions in Ramos cells. Moreover, apoptosis was partly inhibited by transcription inhibitors (actinomycin D) and protein synthesis inhibitors (cycloheximide), suggesting dependency upon new protein synthesis prior to apoptosis. Kinase inhibitors (staurosporin and calphostin C) did not alter the EPA-induced apoptosis. The observed cellular accumulation of superoxide anion following EPA incubation may be important for induction of necrosis in Raji cells. In contrast, none of the other investigated parameters indicated a role of oxidative stress promoted by EPA in the induction of apoptosis in Ramos cells.
本研究聚焦于氧化应激在二十碳五烯酸（EPA）分别诱导淋巴瘤细胞系Raji和Ramos发生坏死或凋亡过程中的作用。为了探究EPA诱导的不同死亡模式，我们评估了一些抗氧化剂和活性氧在这两种细胞系中的重要性。我们观察到，不同的抗氧化剂对EPA对Raji细胞的坏死作用有不同程度的拮抗，并且维生素E可拮抗EPA诱导的该细胞系中超氧阴离子的积累。相反，未观察到抗氧化剂对EPA诱导的Ramos细胞凋亡有影响，且维生素E不能拮抗EPA诱导的Ramos细胞中超氧阴离子的积累。此外，转录抑制剂（放线菌素D）和蛋白质合成抑制剂（环己酰亚胺）可部分抑制凋亡，提示凋亡前依赖新的蛋白质合成。激酶抑制剂（星形孢菌素和钙泊三醇）未改变EPA诱导的凋亡。EPA孵育后观察到的细胞中超氧阴离子的积累可能对Raji细胞坏死的诱导很重要。相比之下，其他所研究的参数均未表明EPA促进的氧化应激在Ramos细胞凋亡诱导中起作用。
